Covid19Phase 2NCT04771000
A Study of Micro Dose Ambrisentan in Hospitalized Patients With Respiratory Insufficiency Due to COVID-19
A Phase 2 study testing Ambrisentan in people with Covid19 and Hypoxemia, run by Noorik Biopharmaceuticals AG at 13 sites in 2 countries.
Trial summary
Patients with COVID-19 frequently develop lower respiratory complications. Difficulty breathing and a low concentration of oxygen in the blood are of concern in patients with COVID-19, as they indicate that the lungs may be significantly affected. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- What is being tested?
- Ambrisentan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 8 Feb 2021to 27 Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject (or legally authorized representative) provides informed consent (written or oral) prior to initiation of any study procedures.
- Male or non-pregnant, non-lactating female. Women of child-bearing potential must have a confirmed negative serum pregnancy test at the time of screening and must use a highly effective contraceptive method throughout the study (such as implants, injectables, hormonal contraceptives and condom, double barrier contraception [i.e., condom + diaphragm/spermicidal gel or foam]) and until one month after completing treatment with the study medication. In the case of hormonal contraception, women should have been on a stable regimen for a minimum of three months before study enrolment. Women not of child-bearing potential include post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy). Men must use an effective contraception method (i.e., condom + diaphragm/spermicidal gel or foam, or vasectomy), and should not donate semen during the study. Men are considered to be fertile from the time of puberty, except for those men with permanent sterility secondary to bilateral orchiectomy.
- At least 18 years of age and not older than 85 years of age at time of enrolment
- Confirmed SARS-CoV-2 infection defined as: Positive Real-Time Polymerase Chain Reaction (RT-PCR) result in sample collected in the 10 days prior to randomisation, OR positive antigenic test result in sample collected in the 10 days prior to randomisation.
- Radiological confirmation of pneumonia.
- Subject receiving low-flow oxzgen supplementation of at least 2 L/min and not more than 15 L/min.
- Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
- Subject (or legally authorized representative) agrees to not participate in any other clinical trial, including clinical trials for the treatment or prevention of COVID-19 or SARS-CoV-2 through Day 30.
Who cannot join
- Subject at a high risk of death, according to investigator's opinion, in the 3 months following enrollment from other causes than Acute Respiratory Distress Syndrome (e.g., severe neurological damage or cancer patients in terminal stages of the disease).
- Subject currently being treated with an endothelin receptor antagonist.
- Subject currently being treated with another pulmonary vasodilator.
- Anticipated need for high-flow oxygen supplementation, non-invasive mechanical ventilation, endotracheal intubation or tracheostomy at the time of screening.
- History of mechanical ventilation (invasive or non-invasive) in the last 7 days.
- Documented history of end-stage liver disease, cirrhosis or idiopathic pulmonary fibrosis (IPF) with or without pulmonary arterial hypertension.
Show all 10Show fewer
- Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3-times the upper limit of normal (ULN).
- Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 96 hours.
- Participation in another interventional clinical trial in the 15 days prior to enrollment.
- Known hypersensitivity to ambrisentan or propylene glycol.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
Spain11 sites
Hospital Universitario de Galdakao-Usansolo
Galdakao, Comunidad de Bizkaia, 48960
Hospital Universitario de Cabueñes
Gijón, Principality of Asturias, 33394
Hospital Universitario Virgen de las Nieves
Granada, Comunidad de Andalucia, 18014
Hospital Universitario San Cecilio
Granada, Comunidad de Andalucia, 18016
Hospital Universitario de Jaén
Jaén, Comunidad de Andalucía, 23007
Hospital Universitario Infanta Leonor
Madrid, 28031
University Hospital 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital de Emergencias Enfermera Isabel Zendal
Madrid, 28055
Hospital Rey Juan Carlos
Móstoles, Madrid, 28933
Complejo Hospitalario de Navarra
Pamplona, Comunidad de Navarra, 31008
Croatia2 sites
General Hopital Zadar
Zadar, 23000
University Hospital for Infectious Diseases Fran Mihaljevic
Zagreb, 10000
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Ambrisentan in Patients With Severe COVID-19
Patients with COVID-19 frequently develop lower respiratory complications. Difficulty breathing and a low concentration of oxygen in the blood are of concern in patients with COVID-19, as they indicate that the lungs may be significantly affected. In some patients, respiratory symptoms may progress to the point where oxygen support is needed (i.e. use of an oxygen prongs, mask or ventilator).
The exact mechanism of why patients with COVID-19 develop low concentrations of oxygen in blood is not fully understood. Some data suggest that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus Disease 2019 (COVID-19), can affect the body's blood vessels directly and extensively. In the lung, blood vessels participate in the absorption of oxygen.
Read more
Endothelin is a potent hormone produced by human blood vessels. When increased, endothelin can result in the narrowing of blood vessels in the lung and decrease the volume of blood flowing through the lungs. This decrease in in blood flow through the lungs may be one of many factors affecting normal lung function. Ambrisentan can block the effects of endothelin in the body, and this could theoretically improve blood flow through the lungs.
This study will evaluate whether ambrisentan, by blocking the effects of the hormone endothelin in the lungs, improves the breathing capacity of patients with COVID-19, increases the concentration of oxygen in the blood and prevents the progression to respiratory failure and death. Ambrisentan is a drug that is currently used to treat patients with pulmonary hypertension, a disease where blood flow through the lungs is decreased.
Subjects participating in this study are those patients hospitalised with severe respiratory symptoms related to COVID-19, and are considered to be at high-risk of developing respiratory complications. Ambrisentan will be administered in the hospital, and will be continued at home for up to 28 days. In this study, ambrisentan will be administered at much lower doses that those used in patients with pulmonary hypertension.
Read the detailed description
This is a randomized, double-blind, placebo-controlled, multi-centre trial to evaluate the safety and efficacy of ambrisentan for the treatment of severe COVID-19. The population consists of hospitalized subjects who have a confirmed SARS-CoV-2 (a coronavirus (CoV) ) infection, are at high-risk of progression to respiratory failure or death and have low oxygen saturation and/or require oxygen supplementation at the time of admission. Pregnant or lactating women will not be allowed to participate in this study given the teratogenic potential of ambrisentan. Subjects requiring mechanical ventilation or intubation at the time of enrolment are considered to have respiratory failure and will not be allowed into the study, as one primary objective of the study is to evaluate the effect of ambrisentan in preventing respiratory failure.
Enrolled subjects will be randomly assigned to the treatment arm or control arm at a 1:1 ratio. In the treatment arm, subjects will receive ambrisentan on top of the standard-of-care. In the control arm, subjects will receive the administration vehicle only (i.e., placebo) and on top of the standard of care. The study medication (ambrisentan or placebo) will be administered for up to 28 days. In the event that the subject is discharged between Day 4 and Day 28, the subject will continue the study treatment at home until completion of the 28-day study medication regimen. Investigators, the Sponsor and the subject will be blinded to the treatment assignment. A Drug Safety Monitoring Board will be monitoring the safety of the study.
- Being tested
- Ambrisentan, Placebo
- Keywords
- Covid19, Hypoxemia, Endothelin, Endothelin receptor antagonist, Ambrisentan, Micro-dose, Acute Respiratory Distress Syndrome (ARDS), Mechanical ventilation, Pulmonary vasodilator, Hypoxic respiratory failure, Respiratory Failure
- Medical subject headings
- COVID-19, Hypoxia, Respiratory Distress Syndrome, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
Also called N-003 (ambrisentan solution)
Endothelin receptor antagonist
PlaceboDrug
Also called Propylene glycol
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan | Experimental | Ambrisentan, 125µg twice a day for up to 28 days Receives: Drug: Ambrisentan |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects alive and not having developed respiratory failure from randomization to Day 14
The number of patients that are alive and have not developed respiratory failure by day 30 after entering the study will be compared between the experimental and placebo arms
Measured: 30 days
Secondary outcomes (13)
Proportion of subjects alive and free of respiratory failure at Day 14 and Day 30
The number of patients that are alive and have not developed respiratory failure on day 14 will will be compared between the experimental and placebo arms
Measured: 14 days and 30 days
Proportion of subjects alive and not requiring oxygen supplementation or higher respiratory support at Day 14.
The number of patients not requiring supplemental oxygen, or any other type of respiratory support at day 14 will be compared between the experimental and placebo arms
Measured: 14 days
Time to hospital discharge (up to Day 30)
The time in days required for subjects to be discharged from the first hospitalisation will be estimated and compared between the experimental and placebo groups
Measured: 30 days
Proportion of subjects admitted to the Intensive Care Unit or High-Dependency Unit (up to Day 30)
The number of patients who qualified for admission or where admitted to an intensive care or a high-dependency unit at any time during the first 30 days after entering the study will be estimated and compared between the experimental and placebo groups
Measured: 30 days
Time until weaning from oxygen therapy (up to Day 30)
The time in days subjects required to breathe independently and without oxygen support will be estimated and compared for the experimental and placebo groups
Measured: 30 days
Time until weaning from respiratory support other than low-flow oxygen supplementation for subjects having developed respiratory failure (up to Day 30)
The time in days subjects required to breathe independently with or without supplemental oxygen will be estimated and compared for the experimental and placebo groups
Measured: 30 days
Change in SpO2/FiO2 from baseline to the time-weighted average obtained on Day 3
The difference in blood oxygen saturation (SpO2) corrected by the inspired fraction of oxygen (FiO2) between baseline and the time-adjusted average calculated for day 3 will be compared between the experimental and placebo arms
Measured: 3 days
Change in SpO2/FiO2 from baseline to the time-weighted average obtained on Day 1
The difference in blood oxygen saturation corrected by the inspired fraction of oxygen between baseline and the time-adjusted average calculated for day 1 will be compared between the experimental and placebo arms
Measured: 1 day
Change in SpO2/FiO2 from baseline to the time-weighted average obtained on Day 2
The difference in blood oxygen saturation corrected by the inspired fraction of oxygen between baseline and the time-adjusted average calculated for day 2 will be compared between the experimental and placebo arms
Measured: 2 days
Proportion of subjects experiencing at least one event of venous thrombosis (specifically deep venous thrombosis or pulmonary embolism) (up to Day 30).
The number of patients who developed thrombosis or pulmonary embolism during the first 30 days after entering the study will be estimated and compared between the experimental and placebo groups
Measured: 30 days
Proportion of subjects by clinical status reported on a 11-point ordinal scale at Day 14 and Day 30
The number of patients classified according to an 11-pont scale on their clinical status at day 14 and day 30 will be calculated and compared between the experimental and placebo groups. The 11-point scale is as follows: Uninfected (0 points), Ambulatory and Asymptomatic (1 point), Symptomatic and independent (2 points), Symptomatic requiring assistance (3 points), Hospitalized with no oxygen therapy (4 points), Hospitalized with oxygen by mask or nasal prongs (5 points), Hospitalized with oxygen by non-invasive ventilation or high flow (6 points), Intubation and mechanical ventilation, PaO2/FiO2 ≥ 150 or SpO2/FiO2 ≥ 200 (7 points), Mechanical ventilation, PaO2/FiO2 <150 (SpO2/FiO2 < 200) or vasopressors (8 points), Mechanical ventilation, PaO2/FiO2 < 150 (SpO2/FiO2 < 200) and vasopressors, dialysis or Extracorporeal Membrane Oxygenation (ECMO) (9 points), Dead (10 points).
Measured: 14 days and 30 days
Time to death due to any cause (up to Day 30)
For those subjects dying in the first 30 days after study entry, the time from study entry to death will be estimated and compared between the experimental and placebo groups
Measured: 30 days
All-cause mortality at Day 30
The number of patients dying during the study observation period independent of the cause of death will be calculated and compared between the experimental and placebo groups.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start8 Feb 2021
- Primary completion27 Feb 2023
- Study completion27 Feb 2023
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noorik Biopharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rok Civljak, MD, Principal investigator, University Hospital for Infectious Diseases Fran Mihaljevic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04771000
- Sponsor's protocol ID
- N-003-CRD008
- Status last verified
- Mar 2023
- First submitted
- 24 Feb 2021
- Last updated
- 21 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Not yet discussed or decided
Publications
Argulian E, Sud K, Vogel B, Bohra C, Garg VP, Talebi S, Lerakis S, Narula J. Right Ventricular Dilation in Hospitalized Patients With COVID-19 Infection. JACC Cardiovasc Imaging. 2020 Nov;13(11):2459-2461. doi: 10.1016/j.jcmg.2020.05.010. Epub 2020 May 15. No abstract available.
PubMed 32426088Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 Jul;8(7):681-686. doi: 10.1016/S2213-2600(20)30243-5. Epub 2020 May 27.
PubMed 32473124Santamarina MG, Boisier D, Contreras R, Baque M, Volpacchio M, Beddings I. COVID-19: a hypothesis regarding the ventilation-perfusion mismatch. Crit Care. 2020 Jul 6;24(1):395. doi: 10.1186/s13054-020-03125-9. No abstract available.
PubMed 32631389Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. No abstract available.
PubMed 32291463Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
PubMed 32171076Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120-128. doi: 10.1056/NEJMoa2015432. Epub 2020 May 21.
PubMed 32437596Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5. Epub 2020 Apr 21. No abstract available.
PubMed 32325026Kalk P, Senf P, Deja M, Petersen B, Busch T, Bauer C, Boemke W, Kaisers U, Hocher B. Inhalation of an endothelin receptor A antagonist attenuates pulmonary inflammation in experimental acute lung injury. Can J Physiol Pharmacol. 2008 Aug;86(8):511-5. doi: 10.1139/Y08-046.
PubMed 18758498Deja M, Busch T, Wolf S, Donaubauer B, Petersen B, Skomrock J, Boemke W, Kaisers U. Inhalation of the endothelin-A receptor antagonist LU-135252 at various doses in experimental acute lung injury. J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S151-5. doi: 10.1097/01.fjc.0000166261.42723.b7.
PubMed 15838267Comellas AP, Briva A. Role of endothelin-1 in acute lung injury. Transl Res. 2009 Jun;153(6):263-71. doi: 10.1016/j.trsl.2009.02.007. Epub 2009 Mar 20.
PubMed 19446279Henry PJ. Respiratory viral infections and the endothelin system. Pulm Pharmacol Ther. 1998 Apr-Jun;11(2-3):133-40. doi: 10.1006/pupt.1998.0127. No abstract available.
PubMed 9918745Carpenter TC, Reeves JT, Durmowicz AG. Viral respiratory infection increases susceptibility of young rats to hypoxia-induced pulmonary edema. J Appl Physiol (1985). 1998 Mar;84(3):1048-54. doi: 10.1152/jappl.1998.84.3.1048.
PubMed 9480968Carpenter TC, Stenmark KR. Endothelin receptor blockade decreases lung water in young rats exposed to viral infection and hypoxia. Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L547-54. doi: 10.1152/ajplung.2000.279.3.L547.
PubMed 10956630Oparil S, Chen SJ, Meng QC, Elton TS, Yano M, Chen YF. Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat. Am J Physiol. 1995 Jan;268(1 Pt 1):L95-100. doi: 10.1152/ajplung.1995.268.1.L95.
PubMed 7840234Maguire JJ, Kuc RE, Davenport AP. Defining the affinity and receptor sub-type selectivity of four classes of endothelin antagonists in clinically relevant human cardiovascular tissues. Life Sci. 2012 Oct 15;91(13-14):681-6. doi: 10.1016/j.lfs.2012.05.008. Epub 2012 May 23.
PubMed 22634326
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Ambrisentan in Patients With Severe COVID-19
- ClinicalTrials.gov ID
- NCT04771000
- Acronym / sponsor ID
- N-003-CRD008
- Keywords
- Covid19, Hypoxemia, Endothelin, Endothelin receptor antagonist, Ambrisentan, Micro-dose, Acute Respiratory Distress Syndrome (ARDS), Mechanical ventilation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Noorik Biopharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- 27 Feb 2023 (actual)
- Study completion
- 27 Feb 2023 (actual)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with COVID-19 frequently develop lower respiratory complications. Difficulty breathing and a low concentration of oxygen in the blood are of concern in patients with COVID-19, as they indicate that the lungs may be significantly affected. In some patients, respiratory symptoms may progress to the point where oxygen support is needed (i.e. use of an oxygen prongs, mask or ventilator).
The exact mechanism of why patients with COVID-19 develop low concentrations of oxygen in blood is not fully understood. Some data suggest that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus Disease 2019 (COVID-19), can affect the body's blood vessels directly and extensively. In the lung, blood vessels participate in the absorption of oxygen.
Endothelin is a potent hormone produced by human blood vessels. When increased, endothelin can result in the narrowing of blood vessels in the lung and decrease the volume of blood flowing through the lungs. This decrease in in blood flow through the lungs may be one of many factors affecting normal lung function. Ambrisentan can block the effects of endothelin in the body, and this could theoretically improve blood flow through the lungs.
This study will evaluate whether ambrisentan, by blocking the effects of the hormone endothelin in the lungs, improves the breathing capacity of patients with COVID-19, increases the concentration of oxygen in the blood and prevents the progression to respiratory failure and death. Ambrisentan is a drug that is currently used to treat patients with pulmonary hypertension, a disease where blood flow through the lungs is decreased.
Subjects participating in this study are those patients hospitalised with severe respiratory symptoms related to COVID-19, and are considered to be at high-risk of developing respiratory complications. Ambrisentan will be administered in the hospital, and will be continued at home for up to 28 days. In this study, ambrisentan will be administered at much lower doses that those used in patients with pulmonary hypertension.
Detailed description
This is a randomized, double-blind, placebo-controlled, multi-centre trial to evaluate the safety and efficacy of ambrisentan for the treatment of severe COVID-19. The population consists of hospitalized subjects who have a confirmed SARS-CoV-2 (a coronavirus (CoV) ) infection, are at high-risk of progression to respiratory failure or death and have low oxygen saturation and/or require oxygen supplementation at the time of admission. Pregnant or lactating women will not be allowed to participate in this study given the teratogenic potential of ambrisentan. Subjects requiring mechanical ventilation or intubation at the time of enrolment are considered to have respiratory failure and will not be allowed into the study, as one primary objective of the study is to evaluate the effect of ambrisentan in preventing respiratory failure.
Enrolled subjects will be randomly assigned to the treatment arm or control arm at a 1:1 ratio. In the treatment arm, subjects will receive ambrisentan on top of the standard-of-care. In the control arm, subjects will receive the administration vehicle only (i.e., placebo) and on top of the standard of care. The study medication (ambrisentan or placebo) will be administered for up to 28 days. In the event that the subject is discharged between Day 4 and Day 28, the subject will continue the study treatment at home until completion of the 28-day study medication regimen. Investigators, the Sponsor and the subject will be blinded to the treatment assignment. A Drug Safety Monitoring Board will be monitoring the safety of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan | Experimental | Drug: AmbrisentanAmbrisentan, 125µg twice a day for up to 28 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject (or legally authorized representative) provides informed consent (written or oral) prior to initiation of any study procedures.
- Male or non-pregnant, non-lactating female. Women of child-bearing potential must have a confirmed negative serum pregnancy test at the time of screening and must use a highly effective contraceptive method throughout the study (such as implants, injectables, hormonal contraceptives and condom, double barrier contraception [i.e., condom + diaphragm/spermicidal gel or foam]) and until one month after completing treatment with the study medication. In the case of hormonal contraception, women should have been on a stable regimen for a minimum of three months before study enrolment. Women not of child-bearing potential include post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy). Men must use an effective contraception method (i.e., condom + diaphragm/spermicidal gel or foam, or vasectomy), and should not donate semen during the study. Men are considered to be fertile from the time of puberty, except for those men with permanent sterility secondary to bilateral orchiectomy.
- At least 18 years of age and not older than 85 years of age at time of enrolment
- Confirmed SARS-CoV-2 infection defined as: Positive Real-Time Polymerase Chain Reaction (RT-PCR) result in sample collected in the 10 days prior to randomisation, OR positive antigenic test result in sample collected in the 10 days prior to randomisation.
- Radiological confirmation of pneumonia.
Key exclusion criteria (10 listed)
- Subject at a high risk of death, according to investigator's opinion, in the 3 months following enrollment from other causes than Acute Respiratory Distress Syndrome (e.g., severe neurological damage or cancer patients in terminal stages of the disease).
- Subject currently being treated with an endothelin receptor antagonist.
- Subject currently being treated with another pulmonary vasodilator.
- Anticipated need for high-flow oxygen supplementation, non-invasive mechanical ventilation, endotracheal intubation or tracheostomy at the time of screening.
- History of mechanical ventilation (invasive or non-invasive) in the last 7 days.
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 |
|---|---|---|
| AmbrisentanAlso: N-003 (ambrisentan solution)Endothelin receptor antagonist | Drug | Ambrisentan |
| PlaceboAlso: Propylene glycolPlacebo | Drug | Placebo |
Primary outcome
Proportion of subjects alive and not having developed respiratory failure from randomization to Day 14
Time frame: 30 days
The number of patients that are alive and have not developed respiratory failure by day 30 after entering the study will be compared between the experimental and placebo arms
13 secondary outcomes
Proportion of subjects alive and free of respiratory failure at Day 14 and Day 30
Time frame: 14 days and 30 days
Proportion of subjects alive and not requiring oxygen supplementation or higher respiratory support at Day 14.
Time frame: 14 days
Time to hospital discharge (up to Day 30)
Time frame: 30 days
Proportion of subjects admitted to the Intensive Care Unit or High-Dependency Unit (up to Day 30)
Time frame: 30 days
Time until weaning from oxygen therapy (up to Day 30)
Time frame: 30 days
Time until weaning from respiratory support other than low-flow oxygen supplementation for subjects having developed respiratory failure (up to Day 30)
Time frame: 30 days
Change in SpO2/FiO2 from baseline to the time-weighted average obtained on Day 3
Time frame: 3 days
Change in SpO2/FiO2 from baseline to the time-weighted average obtained on Day 1
Time frame: 1 day
Change in SpO2/FiO2 from baseline to the time-weighted average obtained on Day 2
Time frame: 2 days
Proportion of subjects experiencing at least one event of venous thrombosis (specifically deep venous thrombosis or pulmonary embolism) (up to Day 30).
Time frame: 30 days
Proportion of subjects by clinical status reported on a 11-point ordinal scale at Day 14 and Day 30
Time frame: 14 days and 30 days
Time to death due to any cause (up to Day 30)
Time frame: 30 days
All-cause mortality at Day 30
Time frame: 30 days
Results and safety
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
- Background: PubMed 32426088Argulian E, Sud K, Vogel B, Bohra C, Garg VP, Talebi S, Lerakis S, Narula J. Right Ventricular Dilation in Hospitalized Patients With COVID-19 Infection. JACC Cardiovasc Imaging. 2020 Nov;13(11):2459-2461. doi: 10.1016/j.jcmg.2020.05.010. Epub 2020 May 15. No abstract available.
- Background: PubMed 32473124Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 Jul;8(7):681-686. doi: 10.1016/S2213-2600(20)30243-5. Epub 2020 May 27.
- Background: PubMed 32631389Santamarina MG, Boisier D, Contreras R, Baque M, Volpacchio M, Beddings I. COVID-19: a hypothesis regarding the ventilation-perfusion mismatch. Crit Care. 2020 Jul 6;24(1):395. doi: 10.1186/s13054-020-03125-9. No abstract available.
- Background: PubMed 32291463Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. No abstract available.
- Background: PubMed 32171076Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
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- Individual participant dataSharing planned: Undecided. Not yet discussed or decided
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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.
Rok Civljak, MD principal investigator
University Hospital for Infectious Diseases Fran Mihaljevic
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ambrisentan in people with Covid19 and Hypoxemia, run by Noorik Biopharmaceuticals AG at 13 sites in 2 countries.
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 8 inclusion and 10 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: stopped early, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain, Croatia. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
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?
Proportion of subjects alive and not having developed respiratory failure from randomization to Day 14 (time frame: 30 days). 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 NCT04771000, which also lists 16 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 21 Mar 2023.