Acute Coronary SyndromePhase 4WILLOW TREENCT03869268
The Impact of Aspirin Dose Modification on the Innate Immune Response - Will Lower Dose Aspirin Therapy Reduce the Response to Endotoxin
A Phase 4 study testing Aspirin and Ticagrelor in people with Acute Coronary Syndrome, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Heart attacks are usually caused by clots in a coronary artery, depriving the heart muscle of blood. Platelets are the main type of blood cell causing clots to form and physicians typically give a combination of two anti-platelet drugs, aspirin and ticagrelor, to treat this. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Coronary Syndrome
- What is being tested?
- Aspirin and Ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 24 Apr 2019to 9 Feb 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post-menopausal)]
- Age between 18 and 65 years inclusive
- Non-smokers
- Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg
- In good health as determined by a medical history, physical examination, vital signs and clinical laboratory test results, including renal and liver function, and full blood count
- Provision of informed consent before any trial-related activity
Who cannot join
- Any history of cancer, diabetes or, in the opinion of the investigator, clinically-significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders
- Any history of either significant multiple drug allergies or known allergy to the study drugs or any medicine chemically related to the study drugs
- A clinically-significant illness within 4 weeks of randomisation
- Any clinically-significant abnormal laboratory test results at screening in the opinion of the investigator
- A supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg
- A supine heart rate at screening, after resting for 5 minutes, outside the range of 50-100 beats/min
Show all 12Show fewer
- Receipt of any prescribed or over-the-counter systemic or topical medication within 48 hours prior to the start of dosing
- Planned or expected requirement, during the next 3 months (at randomisation, or 3 weeks at the start of period 2), for any systemic or topical prescribed drug, or for systemic or topical over-the-counter NSAID, corticosteroid, anthihistamine or any other drug that could affect inflammation, thrombosis or haemostasis in the opinion of the investigator.
- Receipt of an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three weeks preceding the start of dosing. When reconfirming eligibility at the start of period 2, receipt of aspirin, ticagrelor or endotoxin during period 1 of this study will not be counted for this purpose.
- Any donation of blood or plasma in the month preceding the start of dosing.
- A history of alcohol or drug abuse
- Mental incapacity or language barriers that preclude adequate understanding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, South Yorkshire, S5 7AU
About this study
Heart attacks are usually caused by clots in a coronary artery, depriving the heart muscle of blood. Platelets are the main type of blood cell causing clots to form and physicians typically give a combination of two anti-platelet drugs, aspirin and ticagrelor, to treat this. However, aspirin and ticagrelor have effects not just on the platelets but also on the immune system. The investigator has been investigating the effects of different doses of aspirin in heart attack participants when taken alongside ticagrelor, and have found that a new, lower dose of aspirin given twice daily, rather than the usual standard dose once daily, reduces the tendency to bleed whilst on treatment. The investigators are hoping to study the wider effects of different aspirin doses, with and without ticagrelor, and have therefore developed this study.
During the two periods of the study, the investigator will give healthy volunteers a combinations of these medications and then stimulate their immune system, in order to see if the medications affect the immune response. The study will involve a period of medication for 10-14 days followed by a day in hospital stimulating the immune system with an injection into the bloodstream of a substance known as endotoxin, which causes temporary flu-like symptoms, followed by blood and urine tests. The investigator will then repeat the process, after a minimum of five weeks, taking a different medication combination and having a further endotoxin injection. The investigator will also keep in contact by telephone until 2 weeks after the end of the medication to ensure participant remain well.
Read the detailed description
Potential participants will contact the research team in response to advertisement. the research team will then set up a screening appointment in the Clinical Research Facility (CRF) at the Northern general Hospital. They will be offered the chance to be sent a copy of the Participant information sheet for the study before the screening appointment, otherwise they will receive on arrival to the CRF and will be given as much time as they would like to read this.
At the screening appointment (visit 1), a medically qualified member of the research team will discuss with the potential participant the background, rationale, design, requirements and risk of the study. The potential participant will have chance to ask any questions they wish and their understanding of the key points will be checked. If they are then happy to sign the consent form, they will do so and the medically-qualified members of the research team taking consent will also sign this. The participant will receive a copy of the signed form for their records. Once written consent has been obtained, participants will be interviewed to obtain information about their demographic details, medical history and medications. They will undergo a physical examination, have their vital signs and height/weight recorded, and have blood drawn from a vein for safety tests.
At visit 2, which should occur within 14 days of visit 1 but not before the results of the safety blood tests are known, ongoing consent, any new adverse events and medication changes will be recorded. Vital signs will be checked and physical examination performed. The research team will review the results of the safety blood tests and, in combination with information collected at visit 1, determine if the participant meets all the inclusion criteria and none of the exclusion criteria, and therefore whether they can proceed to randomisation, which will be performed using an electronic (online) system designed for this purpose, sealedenvelope.com.
Participants will be randomised to receive one of the following 8 treatment regimens, for 10 days, during the first period of the study:
- no drug
- Ticagrelor 180 milligrams (mg) as a loading dose on the last day
- Aspirin 20 mg BD
- Aspirin 20 mg BD, plus ticagrelor 180 mg as a loading dose on the last day
- Aspirin 75 mg once-daily (OD)
- Aspirin 75 mg, plus ticagrelor 180 mg as a loading dose on the last day
- Aspirin 300 mg OD
- Aspirin 300 mg OD, plus ticagrelor 180 mg as a loading dose on the last day
Participants will receive the supply of study medication for the first period and will be instructed when to take this. Aspirin will be supplied as a soluble powder preparation in 100 mg sachets that will be used to prepare 20 mg, 75 mg and 300 mg doses. If required by the study to take aspirin, they will be trained in preparing the correct dose, provided with written illustrated instructions and appropriate equipment for this. They will have blood drawn and urine collected for baseline tests, and will undergo measurements of the bleeding time, whereby an inflatable cuff (of the type used for measuring blood pressure) is inflated to a low pressure around the arm, 3 small cuts in the skin of the forearm are made using sprung lancets designed to minimise discomfort, and the time taken for the cuts to stop bleeding is measured.
Participants will then take their allocated study treatment for 10-14 days (medication period 1), and will be asked not to take this on the morning of visit 3.
At visit 3, which occur after 10-14 days of study medication, participants will once again attend the CRF, this time for a full day. Ongoing consent, any new relevant adverse events and medication changes will be recorded. Participants will undergo physical examination and check of vital signs to ensure they remain well. An intravenous cannula (of the kind typically used for a 'drip') will be inserted into a vein in each arm. One cannula (cannula A) will be used for blood sampling and the other (cannula B) for injection/infusion throughout the course of the day. Blood will be drawn from cannula A for study tests, bleeding time will be measured and urine collected. Participants will then be asked to take the last dose of study medication for period 1, including, where specified by the protocol, a loading dose of ticagrelor administered in the form of 2 x 90 mg orodispersible tablets. Unused medication will be collected, counted and returned to the Northern General Pharmacy.
30 minutes later, an infusion ('drip') of normal saline will be started through cannula B to ensure participants are well hydrated. This will continue for 3 hours and 30 minutes in total. 30 minutes into the infusion, vital signs will be checked, blood will be sampled from cannula A, bleeding time will be measured and an injection of a weight-adjusted dose of sterile bacterial endotoxin will be given through cannula B.
Further blood for study tests will be drawn 0.5, 1, 1.5, 2, 3, 4 and 6 hours after the endotoxin injection. Urine will be collected 1, 2, 4 and 6 hours after the endotoxin injection, Bleeding time will be measured 3 hours after the endotoxin injection. From the time of endotoxin administration until 6 hours after it, participants will be connected to a continuous cardiac monitor, and vital signs will be checked at 0.5, 1, 1.5, 2, 3, 4 and 6 hours after the endotoxin injection. Any reportable adverse events will be recorded throughout the day. At the end of the day (6 hours after endotoxin injection) if feeling well participants will be allowed home, but if there are any concerns arrangements will be made for them to stay later, if necessary overnight, within the CRF or a ward of the Northern General Hospital.
The day after visit 3, participants will be contacted by telephone by a member of the research team (visit 4). Ongoing consent, any new relevant adverse events and medication changes will be recorded. If there are any concerns raised by the participant or investigator arrangements will be made for an in-person review by a medically qualified member of the research team in the CRF.
There will then be a break in study medication of at least five weeks. This is to ensure that any effects of the endotoxin and/or study medication have completely worn off before the next stage of the trial. At 10-14 days after visit 3, participants will be contacted by telephone by a member of the research team (visit 4). Ongoing consent, any new relevant adverse events and medication changes will be recorded. If there are any concerns raised by the participant or investigator arrangements will be made for an in-person review by a medically qualified member of the research team in the CRF.
At visit 6, participants will attend for a clinic visit in the CRF. Ongoing consent, new relevant events and medications changes will be recorded. Vital signs will be checked, physical examination performed and safety blood tests taken. A new set of medication will be provided to the participant, with appropriate training in aspirin dosing if needed. The medication that the participant will be asked to take for the next 10-14 days (medication period 2) will be determined by what they were allocated in medication period 1:
- If received no drug in period 1, to receive no aspirin in period 2 but receive a loading dose of 180 mg ticagrelor on the last day of period 2
- If received no aspirin but received a loading dose of 180 mg ticagrelor on the last day of period 1, to receive no drug in period 2
- If received aspirin 20 mg BD but no ticagrelor in period 1, to receive aspirin 20mg BD in period 2 plus a loading dose of 180 mg ticagrelor on the last day of period 2
- If received aspirin 20 mg BD plus a loading dose of 180 mg ticagrelor on the last day of period 1, to receive aspirin 20 mg BD and no ticagrelor in period 2.
- If received aspirin 75 mg OD but no ticagrelor in period 1, to receive aspirin 75 mg OD in period 2 plus a loading dose of 180 mg ticagrelor on the last day of period 2
- If received aspirin 75 mg OD plus a loading dose of 180 mg ticagrelor on the last day of period 1, to receive aspirin 75 mg OD and no ticagrelor in period 2.
- If received aspirin 300 mg OD but no ticagrelor in period 1, to receive aspirin 300 mg OD in period 2 plus a loading dose of 180 mg ticagrelor on the last day of period 2
- If received aspirin 300 mg OD plus a loading dose of 180 mg ticagrelor on the last day of period 1, to receive aspirin 300 mg OD and no ticagrelor in period 2.
Participants will then take their allocated study treatment for 10-14 days (medication period 2) and will be asked not to take this on the morning of visit 7.
Visits 7, 8 and 9 will be another full day visit to the CRF followed by a telephone call the next day and after 10-14 days. These will follow exactly the same process as visit 3, 4 and 5. At this point their involvement in the study will end and they will be thanked for their participation.
- Conditions
- Acute Coronary Syndrome
- Being tested
- Aspirin, Ticagrelor
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Aspirin will be allocated in different doses and will be used in conjunction with ticagrelor depending on the arm of the trial the participant is randomised to. The different doses are as follows: 20 mg, 75 mg and 300 mg.
TicagrelorDrug
Ticagrelor will be allocated as a single loading dose of 180 mg (2 x 90 mg orodispersible tablets) and will be used in conjunction with aspirin depending on the arm of the trial the participant is randomised to.
| Study group | Role | What they receive |
|---|---|---|
| No Drug | Active comparator | Patients will be randomised to receive no drug for the first medication period (10 days).
Patient will then be allocated to receive ticagrelor 90mg twice daily for the second medication period (10 days) Receives: Drug: Ticagrelor |
| Ticagrelor 180 mg | Active comparator | Participants will be randomised to receive loading dose of ticagrelor 180 mg on the last day of the first medication period (10-14 days).
Participants will then be allocated to receive no aspirin but a loading dose of ticagrelor 180 mg on the last day of treatment for the second medication period (10-14 days). Receives: Drug: Ticagrelor |
| Aspirin 20mg | Active comparator | Participants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10 days).
Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. Receives: Drug: Aspirin; Drug: Ticagrelor |
| Aspirin 20 mg & Ticagrelor 180 mg | Active comparator | Participants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10-14 days).
Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. Receives: Drug: Aspirin; Drug: Ticagrelor |
| Aspirin 75 mg | Active comparator | Participants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days).
Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. Receives: Drug: Aspirin; Drug: Ticagrelor |
| Aspirin 75 mg & Ticagrelor 180 mg | Active comparator | Participants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days). Receives: Drug: Aspirin; Drug: Ticagrelor |
| Aspirin 300 mg | Active comparator | Participants will be randomised to receive aspirin 300 mg once daily for the first medication period (10 days).
Participants will then be allocated to receive aspirin 300 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. Receives: Drug: Aspirin; Drug: Ticagrelor |
| Aspirin 300 mg & Ticagrelor 180 mg | Active comparator | Participants will be randomised to receive aspirin 300 mg once daily for the first medication period (10-14 days) plus a loading dose of ticagrelor 180 mg on the last day of the period.
Participants will then be allocated to receive aspirin 300 mg once daily for the second medicaion period (10-14 days). Receives: Drug: Aspirin; Drug: Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess Inflammatory Response to Intravenous Endotoxin
plasma TNF-α at 2 hours post-injection of 2 ng/kg endotoxin compared between participants receiving no IMP, aspirin (Aspirin lysine) 20 mg BD, aspirin (Aspirin lysine) 75 mg OD and aspirin (Aspirin lysine) 300 mg OD.
Measured: 2 hours post endotoxin injection
Secondary outcomes (3)
Serum CRP Changes
Change in serum CRP from 0 to 6 hours after endotoxin administration
Measured: 0 to 6 hours after endotoxin administration
Leukocyte Count
Leukocyte count, from 0 to 6 hours after endotoxin administration
Measured: 0 to 6 hours after endotoxin administration
Serum TXB2
Serum TXB2 from 0 to 6 hours after endotoxin administration
Measured: 0 to 6 hours after endotoxin administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2019
- Study start24 Apr 2019
- Primary completion10 Dec 2021
- Study completion9 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This trial is a randomised controlled hybrid parallel-group and crossover study.
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03869268
- Sponsor's protocol ID
- STH20370
- Acronym
- WILLOW TREE
- Status last verified
- Jul 2025
- First submitted
- 4 Dec 2018
- Last updated
- 11 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jackson SP. Arterial thrombosis--insidious, unpredictable and deadly. Nat Med. 2011 Nov 7;17(11):1423-36. doi: 10.1038/nm.2515.
PubMed 22064432Luc G, Bard JM, Juhan-Vague I, Ferrieres J, Evans A, Amouyel P, Arveiler D, Fruchart JC, Ducimetiere P; PRIME Study Group. C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME Study. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1255-61. doi: 10.1161/01.ATV.0000079512.66448.1D. Epub 2003 May 29.
PubMed 12775578Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267-315. doi: 10.1093/eurheartj/ehv320. Epub 2015 Aug 29. No abstract available.
PubMed 26320110Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC); Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619. doi: 10.1093/eurheartj/ehs215. Epub 2012 Aug 24. No abstract available.
PubMed 22922416Solari HP, Ventura MP, Orellana ME, Novais GA, Cheema DP, Burnier MN Jr. Histopathological study of lesions of the caruncle: a 15-year single center review. Diagn Pathol. 2009 Aug 31;4:29. doi: 10.1186/1746-1596-4-29.
PubMed 19719846Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.
PubMed 28845751Thomas MR, Outteridge SN, Ajjan RA, Phoenix F, Sangha GK, Faulkner RE, Ecob R, Judge HM, Khan H, West LE, Dockrell DH, Sabroe I, Storey RF. Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model. Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2562-70. doi: 10.1161/ATVBAHA.115.306528. Epub 2015 Oct 29.
PubMed 26515417Patrono C, Morais J, Baigent C, Collet JP, Fitzgerald D, Halvorsen S, Rocca B, Siegbahn A, Storey RF, Vilahur G. Antiplatelet Agents for the Treatment and Prevention of Coronary Atherothrombosis. J Am Coll Cardiol. 2017 Oct 3;70(14):1760-1776. doi: 10.1016/j.jacc.2017.08.037.
PubMed 28958334Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994 May 5;330(18):1287-94. doi: 10.1056/NEJM199405053301808. No abstract available.
PubMed 8145785Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988 Aug 13;2(8607):349-60.
PubMed 2899772Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R; Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008 Oct 16;337:a1840. doi: 10.1136/bmj.a1840.
PubMed 18927173Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010 Jun 22;121(24):2694-701. doi: 10.1161/CIR.0b013e3181e3b133. Epub 2010 May 27. No abstract available.
PubMed 20508178Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S, Saito Y; Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008 Nov 12;300(18):2134-41. doi: 10.1001/jama.2008.623. Epub 2008 Nov 9.
PubMed 18997198Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, Sugawara M, Ando K, Murata M, Yokoyama K, Ishizuka N. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014 Dec 17;312(23):2510-20. doi: 10.1001/jama.2014.15690.
PubMed 25401325Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, Howard G, Pearson TA, Rothwell PM, Ruilope LM, Tendera M, Tognoni G; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018 Sep 22;392(10152):1036-1046. doi: 10.1016/S0140-6736(18)31924-X. Epub 2018 Aug 26.
PubMed 30158069
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Aspirin Dose Modification on the Innate Immune Response - Will Lower Dose Aspirin Therapy Reduce the Response to Endotoxin
- ClinicalTrials.gov ID
- NCT03869268
- Acronym / sponsor ID
- WILLOW TREE / STH20370
- Conditions
- Acute Coronary Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- 24 Apr 2019 (actual)
- Primary completion
- 10 Dec 2021 (actual)
- Study completion
- 9 Feb 2023 (actual)
- First posted
- 11 Mar 2019 (actual)
- Results
- Posted 11 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heart attacks are usually caused by clots in a coronary artery, depriving the heart muscle of blood. Platelets are the main type of blood cell causing clots to form and physicians typically give a combination of two anti-platelet drugs, aspirin and ticagrelor, to treat this. However, aspirin and ticagrelor have effects not just on the platelets but also on the immune system. The investigator has been investigating the effects of different doses of aspirin in heart attack participants when taken alongside ticagrelor, and have found that a new, lower dose of aspirin given twice daily, rather than the usual standard dose once daily, reduces the tendency to bleed whilst on treatment. The investigators are hoping to study the wider effects of different aspirin doses, with and without ticagrelor, and have therefore developed this study.
During the two periods of the study, the investigator will give healthy volunteers a combinations of these medications and then stimulate their immune system, in order to see if the medications affect the immune response. The study will involve a period of medication for 10-14 days followed by a day in hospital stimulating the immune system with an injection into the bloodstream of a substance known as endotoxin, which causes temporary flu-like symptoms, followed by blood and urine tests. The investigator will then repeat the process, after a minimum of five weeks, taking a different medication combination and having a further endotoxin injection. The investigator will also keep in contact by telephone until 2 weeks after the end of the medication to ensure participant remain well.
Detailed description
Potential participants will contact the research team in response to advertisement. the research team will then set up a screening appointment in the Clinical Research Facility (CRF) at the Northern general Hospital. They will be offered the chance to be sent a copy of the Participant information sheet for the study before the screening appointment, otherwise they will receive on arrival to the CRF and will be given as much time as they would like to read this.
At the screening appointment (visit 1), a medically qualified member of the research team will discuss with the potential participant the background, rationale, design, requirements and risk of the study. The potential participant will have chance to ask any questions they wish and their understanding of the key points will be checked. If they are then happy to sign the consent form, they will do so and the medically-qualified members of the research team taking consent will also sign this. The participant will receive a copy of the signed form for their records. Once written consent has been obtained, participants will be interviewed to obtain information about their demographic details, medical history and medications. They will undergo a physical examination, have their vital signs and height/weight recorded, and have blood drawn from a vein for safety tests.
At visit 2, which should occur within 14 days of visit 1 but not before the results of the safety blood tests are known, ongoing consent, any new adverse events and medication changes will be recorded. Vital signs will be checked and physical examination performed. The research team will review the results of the safety blood tests and, in combination with information collected at visit 1, determine if the participant meets all the inclusion criteria and none of the exclusion criteria, and therefore whether they can proceed to randomisation, which will be performed using an electronic (online) system designed for this purpose, sealedenvelope.com.
Participants will be randomised to receive one of the following 8 treatment regimens, for 10 days, during the first period of the study:
- no drug
- Ticagrelor 180 milligrams (mg) as a loading dose on the last day
- Aspirin 20 mg BD
- Aspirin 20 mg BD, plus ticagrelor 180 mg as a loading dose on the last day
- Aspirin 75 mg once-daily (OD)
- Aspirin 75 mg, plus ticagrelor 180 mg as a loading dose on the last day
- Aspirin 300 mg OD
- Aspirin 300 mg OD, plus ticagrelor 180 mg as a loading dose on the last day
Participants will receive the supply of study medication for the first period and will be instructed when to take this. Aspirin will be supplied as a soluble powder preparation in 100 mg sachets that will be used to prepare 20 mg, 75 mg and 300 mg doses. If required by the study to take aspirin, they will be trained in preparing the correct dose, provided with written illustrated instructions and appropriate equipment for this. They will have blood drawn and urine collected for baseline tests, and will undergo measurements of the bleeding time, whereby an inflatable cuff (of the type used for measuring blood pressure) is inflated to a low pressure around the arm, 3 small cuts in the skin of the forearm are made using sprung lancets designed to minimise discomfort, and the time taken for the cuts to stop bleeding is measured.
Participants will then take their allocated study treatment for 10-14 days (medication period 1), and will be asked not to take this on the morning of visit 3.
At visit 3, which occur after 10-14 days of study medication, participants will once again attend the CRF, this time for a full day. Ongoing consent, any new relevant adverse events and medication changes will be recorded. Participants will undergo physical examination and check of vital signs to ensure they remain well. An intravenous cannula (of the kind typically used for a 'drip') will be inserted into a vein in each arm. One cannula (cannula A) will be used for blood sampling and the other (cannula B) for injection/infusion throughout the course of the day. Blood will be drawn from cannula A for study tests, bleeding time will be measured and urine collected. Participants will then be asked to take the last dose of study medication for period 1, including, where specified by the protocol, a loading dose of ticagrelor administered in the form of 2 x 90 mg orodispersible tablets. Unused medication will be collected, counted and returned to the Northern General Pharmacy.
30 minutes later, an infusion ('drip') of normal saline will be started through cannula B to ensure participants are well hydrated. This will continue for 3 hours and 30 minutes in total. 30 minutes into the infusion, vital signs will be checked, blood will be sampled from cannula A, bleeding time will be measured and an injection of a weight-adjusted dose of sterile bacterial endotoxin will be given through cannula B.
Further blood for study tests will be drawn 0.5, 1, 1.5, 2, 3, 4 and 6 hours after the endotoxin injection. Urine will be collected 1, 2, 4 and 6 hours after the endotoxin injection, Bleeding time will be measured 3 hours after the endotoxin injection. From the time of endotoxin administration until 6 hours after it, participants will be connected to a continuous cardiac monitor, and vital signs will be checked at 0.5, 1, 1.5, 2, 3, 4 and 6 hours after the endotoxin injection. Any reportable adverse events will be recorded throughout the day. At the end of the day (6 hours after endotoxin injection) if feeling well participants will be allowed home, but if there are any concerns arrangements will be made for them to stay later, if necessary overnight, within the CRF or a ward of the Northern General Hospital.
The day after visit 3, participants will be contacted by telephone by a member of the research team (visit 4). Ongoing consent, any new relevant adverse events and medication changes will be recorded. If there are any concerns raised by the participant or investigator arrangements will be made for an in-person review by a medically qualified member of the research team in the CRF.
There will then be a break in study medication of at least five weeks. This is to ensure that any effects of the endotoxin and/or study medication have completely worn off before the next stage of the trial. At 10-14 days after visit 3, participants will be contacted by telephone by a member of the research team (visit 4). Ongoing consent, any new relevant adverse events and medication changes will be recorded. If there are any concerns raised by the participant or investigator arrangements will be made for an in-person review by a medically qualified member of the research team in the CRF.
At visit 6, participants will attend for a clinic visit in the CRF. Ongoing consent, new relevant events and medications changes will be recorded. Vital signs will be checked, physical examination performed and safety blood tests taken. A new set of medication will be provided to the participant, with appropriate training in aspirin dosing if needed. The medication that the participant will be asked to take for the next 10-14 days (medication period 2) will be determined by what they were allocated in medication period 1:
- If received no drug in period 1, to receive no aspirin in period 2 but receive a loading dose of 180 mg ticagrelor on the last day of period 2
- If received no aspirin but received a loading dose of 180 mg ticagrelor on the last day of period 1, to receive no drug in period 2
- If received aspirin 20 mg BD but no ticagrelor in period 1, to receive aspirin 20mg BD in period 2 plus a loading dose of 180 mg ticagrelor on the last day of period 2
- If received aspirin 20 mg BD plus a loading dose of 180 mg ticagrelor on the last day of period 1, to receive aspirin 20 mg BD and no ticagrelor in period 2.
- If received aspirin 75 mg OD but no ticagrelor in period 1, to receive aspirin 75 mg OD in period 2 plus a loading dose of 180 mg ticagrelor on the last day of period 2
- If received aspirin 75 mg OD plus a loading dose of 180 mg ticagrelor on the last day of period 1, to receive aspirin 75 mg OD and no ticagrelor in period 2.
- If received aspirin 300 mg OD but no ticagrelor in period 1, to receive aspirin 300 mg OD in period 2 plus a loading dose of 180 mg ticagrelor on the last day of period 2
- If received aspirin 300 mg OD plus a loading dose of 180 mg ticagrelor on the last day of period 1, to receive aspirin 300 mg OD and no ticagrelor in period 2.
Participants will then take their allocated study treatment for 10-14 days (medication period 2) and will be asked not to take this on the morning of visit 7.
Visits 7, 8 and 9 will be another full day visit to the CRF followed by a telephone call the next day and after 10-14 days. These will follow exactly the same process as visit 3, 4 and 5. At this point their involvement in the study will end and they will be thanked for their participation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
- Model description
- This trial is a randomised controlled hybrid parallel-group and crossover study.
| Arm | Type | Receives |
|---|---|---|
| No Drug | Active comparator | Drug: TicagrelorPatients will be randomised to receive no drug for the first medication period (10 days). Patient will then be allocated to receive ticagrelor 90mg twice daily for the second medication period (10 days) |
| Ticagrelor 180 mg | Active comparator | Drug: TicagrelorParticipants will be randomised to receive loading dose of ticagrelor 180 mg on the last day of the first medication period (10-14 days). Participants will then be allocated to receive no aspirin but a loading dose of ticagrelor 180 mg on the last day of treatment for the second medication period (10-14 days). |
| Aspirin 20mg | Active comparator | Drug: Aspirin, Drug: TicagrelorParticipants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10 days). Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. |
| Aspirin 20 mg & Ticagrelor 180 mg | Active comparator | Drug: Aspirin, Drug: TicagrelorParticipants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10-14 days). Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. |
| Aspirin 75 mg | Active comparator | Drug: Aspirin, Drug: TicagrelorParticipants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days). Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. |
| Aspirin 75 mg & Ticagrelor 180 mg | Active comparator | Drug: Aspirin, Drug: TicagrelorParticipants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days). |
| Aspirin 300 mg | Active comparator | Drug: Aspirin, Drug: TicagrelorParticipants will be randomised to receive aspirin 300 mg once daily for the first medication period (10 days). Participants will then be allocated to receive aspirin 300 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period. |
| Aspirin 300 mg & Ticagrelor 180 mg | Active comparator | Drug: Aspirin, Drug: TicagrelorParticipants will be randomised to receive aspirin 300 mg once daily for the first medication period (10-14 days) plus a loading dose of ticagrelor 180 mg on the last day of the period. Participants will then be allocated to receive aspirin 300 mg once daily for the second medicaion period (10-14 days). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post-menopausal)]
- Age between 18 and 65 years inclusive
- Non-smokers
- Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg
- In good health as determined by a medical history, physical examination, vital signs and clinical laboratory test results, including renal and liver function, and full blood count
Key exclusion criteria (12 listed)
- Any history of cancer, diabetes or, in the opinion of the investigator, clinically-significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders
- Any history of either significant multiple drug allergies or known allergy to the study drugs or any medicine chemically related to the study drugs
- A clinically-significant illness within 4 weeks of randomisation
- Any clinically-significant abnormal laboratory test results at screening in the opinion of the investigator
- A supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAspirin will be allocated in different doses and will be used in conjunction with ticagrelor depending on the arm of the trial the participant is randomised to. The different doses are as follows: 20 mg, 75 mg and 300 mg. | Drug | Aspirin 20 mg & Ticagrelor 180 mg, Aspirin 20mg, Aspirin 300 mg, Aspirin 300 mg & Ticagrelor 180 mg, Aspirin 75 mg, Aspirin 75 mg & Ticagrelor 180 mg |
| TicagrelorTicagrelor will be allocated as a single loading dose of 180 mg (2 x 90 mg orodispersible tablets) and will be used in conjunction with aspirin depending on the arm of the trial the participant is randomised to. | Drug | Aspirin 20 mg & Ticagrelor 180 mg, Aspirin 20mg, Aspirin 300 mg, Aspirin 300 mg & Ticagrelor 180 mg, Aspirin 75 mg, Aspirin 75 mg & Ticagrelor 180 mg, No Drug, Ticagrelor 180 mg |
Primary outcome
Assess Inflammatory Response to Intravenous Endotoxin
Time frame: 2 hours post endotoxin injection
plasma TNF-α at 2 hours post-injection of 2 ng/kg endotoxin compared between participants receiving no IMP, aspirin (Aspirin lysine) 20 mg BD, aspirin (Aspirin lysine) 75 mg OD and aspirin (Aspirin lysine) 300 mg OD.
3 secondary outcomes
Serum CRP Changes
Time frame: 0 to 6 hours after endotoxin administration
Leukocyte Count
Time frame: 0 to 6 hours after endotoxin administration
Serum TXB2
Time frame: 0 to 6 hours after endotoxin administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22064432Jackson SP. Arterial thrombosis--insidious, unpredictable and deadly. Nat Med. 2011 Nov 7;17(11):1423-36. doi: 10.1038/nm.2515.
- Background: PubMed 12775578Luc G, Bard JM, Juhan-Vague I, Ferrieres J, Evans A, Amouyel P, Arveiler D, Fruchart JC, Ducimetiere P; PRIME Study Group. C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME Study. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1255-61. doi: 10.1161/01.ATV.0000079512.66448.1D. Epub 2003 May 29.
- Background: PubMed 26320110Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267-315. doi: 10.1093/eurheartj/ehv320. Epub 2015 Aug 29. No abstract available.
- Background: PubMed 22922416Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC); Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619. doi: 10.1093/eurheartj/ehs215. Epub 2012 Aug 24. No abstract available.
- Background: PubMed 19719846Solari HP, Ventura MP, Orellana ME, Novais GA, Cheema DP, Burnier MN Jr. Histopathological study of lesions of the caruncle: a 15-year single center review. Diagn Pathol. 2009 Aug 31;4:29. doi: 10.1186/1746-1596-4-29.
- Background: PubMed 28845751Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.
- Background: PubMed 26515417Thomas MR, Outteridge SN, Ajjan RA, Phoenix F, Sangha GK, Faulkner RE, Ecob R, Judge HM, Khan H, West LE, Dockrell DH, Sabroe I, Storey RF. Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model. Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2562-70. doi: 10.1161/ATVBAHA.115.306528. Epub 2015 Oct 29.
- Background: PubMed 28958334Patrono C, Morais J, Baigent C, Collet JP, Fitzgerald D, Halvorsen S, Rocca B, Siegbahn A, Storey RF, Vilahur G. Antiplatelet Agents for the Treatment and Prevention of Coronary Atherothrombosis. J Am Coll Cardiol. 2017 Oct 3;70(14):1760-1776. doi: 10.1016/j.jacc.2017.08.037.
- Background: PubMed 8145785Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994 May 5;330(18):1287-94. doi: 10.1056/NEJM199405053301808. No abstract available.
- Background: PubMed 2899772Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988 Aug 13;2(8607):349-60.
- Background: PubMed 18927173Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R; Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008 Oct 16;337:a1840. doi: 10.1136/bmj.a1840.
- Background: PubMed 20508178Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010 Jun 22;121(24):2694-701. doi: 10.1161/CIR.0b013e3181e3b133. Epub 2010 May 27. No abstract available.
Related trials for Acute Coronary Syndrome
Recruiting
CT Stress Myocardial Perfusion, Fractional Flow Reserve and Angiography in Patients With Stable Chest Pain Syndromes
Coronary Artery Disease, Chest Syndrome
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
RecruitingPhase 4
Early Single Antiplatelet Therapy After IVUS-Guided PCI in Acute Coronary Syndrome
Acute Coronary Syndromes, STEMI
Recruiting
AI-Assisted Interpretation of Cardiac CT in the Emergency Department
Chest Pain, Acute Coronary Syndrome
Enrolling by invitation
Optical Coherence Tomography in Acute Vessel Evaluation
Ischemic Heart Disease, Ischemic Coronary Artery Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aspirin and Ticagrelor in people with Acute Coronary Syndrome, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess Inflammatory Response to Intravenous Endotoxin (time frame: 2 hours post endotoxin injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03869268, which also lists 36 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.