Myocardial Reperfusion InjuryPhase 2CAPRINCT02390674
Ciclosporin to Reduce Reperfusion Injury in Primary PCI
A Phase 2 study testing Ciclosporin and Saline in people with Myocardial Reperfusion Injury, run by Newcastle-upon-Tyne Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
Routine primary percutaneous coronary intervention (PPCI) for a heart attack involves opening a blocked artery with a balloon then inserting a metal scaffold (stent) to hold the artery open. During this procedure inflammation can occur causing further damage to the heart. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Reperfusion Injury
- What is being tested?
- Ciclosporin and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2015to 11 Nov 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting with acute myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI)
- Age above 18 years
- Presenting within 6 hours of the onset chest pain and ST segment elevation. The culprit coronary artery has to be a major coronary artery with a diameter of at least 3mm and has to be proximally occluded (TIMI flow grade 0-1) at the time of admission coronary angiography
Who cannot join
- Patients with any disorder associated with immunological dysfunction (acute or chronic inflammatory or neoplastic co-existing disease, known positive serology for HIV, or hepatitis)
- Clinically unstable patients (haemodynamically unstable, cardiogenic shock, unconscious patients)
- Patients with evidence of coronary collaterals to the infarct area
- Patients with an open (TIMI > 1) culprit coronary artery at the time of angiography.
- Previous myocardial infarction
- Previous thrombolytic therapy
Show all 22Show fewer
- Patients with known hypersensitivity to ciclosporin or to egg, peanut or soya-bean proteins.
- Patients with known renal insufficiency (either known glomerular filtration rate (GFR) <30 ml/min/1.73m2) or current medical care for severe renal insufficiency.
- Known liver insufficiency
- Uncontrolled hypertension (>180/110 mmHg)
- Patients treated with any compound containing hypericum perforatum, stiripentol, Aliskiren, Bosentan or Rosuvastatin or with an active treatment that might modify blood concentration of ciclosporin.
- Female patients currently pregnant or women of childbearing age who are not using contraception (verbal diagnosis). Female patients of childbearing potential who are using contraception but are subsequently found to have a positive urine pregnancy test (pregnancy test performed as soon as reasonably practicable after investigational medicinal product (IMP) administration).
- Contraindication to cardiac MRI:
- Pacemaker
- Implantable defibrillator
- Patients unable to undergo cardiac MRI for any of the following reasons:
- Frailty - as judged by the clinician. Frailty is defined as meeting three out of the five following criteria: low grip strength, low energy, slowed walking speed, low physical activity and/or unintentional weight loss. Due to the tight time constraints and emergency setting of this trial the clinician cannot test all these parameters and will need to exercise their judgment.
- Claustrophobic - patients who cannot take elevators or who are afraid of narrow or enclosed spaces.
- Breathlessness - patients who suffer from breathlessness at rest or low exercise level (e.g. while walking on the level).
- Use of other investigational study drugs within 30 days prior to trial entry (defined as date of randomisation into trial). Co-enrolment with other studies is not allowed.
- Lack of capacity to give initial verbal consent
- Life expectancy <1year due to non-cardiac illness
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Newcastle Clinical Trials Unit
Newcastle upon Tyne, Tyne and Wear, NE2 4AE
About this study
Official title: Evaluating the Effectiveness of Intravenous Ciclosporin on Reducing Reperfusion Injury in Patients Undergoing Primary Percutaneous Intervention: a Double-blind Randomised Controlled Trial
Routine primary percutaneous coronary intervention (PPCI) for a heart attack involves opening a blocked artery with a balloon then inserting a metal scaffold (stent) to hold the artery open. During this procedure inflammation can occur causing further damage to the heart. The objective of this trial is to determine whether administration of the drug ciclosporin prior to PPCI reduces the amount of damage to the heart relative to treatment with placebo. The damage to the heart is assessed after 12 weeks by an magnetic resonance imaging (MRI) scan. Patients are followed-up after 12 months participation in the study.
This is a single centre study looking to recruit 68 patients.
Read the detailed description
Coronary heart disease is a condition in which the supply of blood and oxygen to the heart is reduced due to the narrowing of the arteries supplying the heart. A heart attack is caused when one of these arteries becomes blocked. Modern treatment for a heart attack is called primary percutaneous coronary intervention (PPCI). PPCI involves opening the blocked artery with a balloon and placing a stent (a small metal tube) in the artery to hold it open.
Research has shown that after opening the blocked artery, inflammation develops within the heart. This inflammation is generated by the immune system. Initial studies have suggested that certain immune system cells (T-cells) may be involved in causing much of the damage that occurs in the heart following a heart attack. The drug ciclosporin temporarily inhibits the immune system and it has been shown in a small number of patients that it reduces the size of the heart attack. The aim of this clinical trial is to investigate in a larger number of patients whether the size of the heart attack is reduced in patients treated with the drug ciclosporin prior to PPCI relative to patients treated with a placebo (saline).
To participate in the trial you must be having a large heart attack (STEMI - ST segment elevation myocardial infarction) and be undergoing a PPCI to unblock your artery. You must also be aged over 18 years. You will be randomised to receive either a single dose of the drug ciclosporin or placebo before your blocked artery is opened. Half the people will get the drug ciclosporin. This randomisation will enable us to compare the results to see whether treatment with ciclosporin reduces the size of the heart attack compared with placebo.
There may be no immediate benefit from taking part in the trial but the information we get from this trial will help improve the treatment of people having a heart attack in the future. As far as we know there are no disadvantages of taking part in the trial. If you are randomised to the 'drug' group, there is a very small risk of side effects from ciclosporin, such as high blood pressure and slight worsening of kidney function. We do not expect any side effects as the ciclosporin is only given once in the trial. On rare occasions allergic reactions have been observed. If any ciclosporin-related side effects were to occur, they would be expected soon after the drug was administered.
This is a single centre, randomised, double-blind, parallel group, placebo-controlled phase II/III trial comparing the efficacy of ciclosporin versus placebo in 68 patients with acute myocardial infarction undergoing PPCI. The trial is set in a tertiary care centre (Freeman Hospital, Newcastle upon Tyne, UK) and patients will be recruited over a period of 18 months. The trial is designed to show superiority regarding its primary endpoint. During initial hospitalisation following myocardial infarction, treatment is given once prior to performing the PPCI in the catheter laboratory. The duration of study for each patient is 12 months until final follow-up (12 weeks randomised controlled trial (RCT) followed by 9 months study follow-up). Should treatment with ciclosporin look promising, a larger trial will be designed to evaluate ciclosporin treatment fully. In contrast to the previous study, this trial is not restricted to anterior STEMI patients. It will also analyse changes in inflammatory response following reperfusion and will use MRI (current gold standard) in every patient to quantify infarct size, ejection fraction and microvascular obstruction.
- Conditions
- Myocardial Reperfusion Injury
- Being tested
- Ciclosporin, Saline
- Medical subject headings
- Myocardial Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiclosporinDrug
Also called Sandimmun
Comparison between ciclosporin and placebo
SalineDrug
| Study group | Role | What they receive |
|---|---|---|
| Ciclosporin | Active comparator | Single intravenous administration of ciclosporin (2.5mg per kilogram body weight) immediately prior to reperfusion during primary percutaneous coronary intervention. Ciclosporin is dissolved in saline (maximum concentration 2.5mg per millilitre) Receives: Drug: Ciclosporin |
| Saline | Placebo comparator | Single intravenous administration of placebo (saline) immediately prior to reperfusion during primary percutaneous coronary intervention Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in infarct size
Change in infarct size 12 weeks post-PPCI as measured by cardiac MRI
Measured: 12 weeks after primary percutaneous coronary intervention (PPCI)
Secondary outcomes (3)
Change in microvascular obstruction
Microvascular obstruction after 2-7 days as measured by a single cardiac MRI scan
Measured: Measured once between day 2 and day 7 after PPCI
Change in salvage index
Salvage index after 2-7 days as measured by a single cardiac MRI scan
Measured: Measured once between day 2 and day 7 after PPCI
Change in T lymphocyte count
Change in T lymphocyte counts relative to baseline at 5, 15, 30, 60 and 90 minutes post-reperfusion
Measured: 5, 15, 30, 60 and 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionApr 2017
- Study completion11 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial Reperfusion InjuryStudies 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, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Newcastle University
- Responsible party
- Sponsor
- Investigators
- Ioakim Spyridopoulos, PhD, MD, Principal investigator, Newcastle University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02390674
- Sponsor's protocol ID
- R&D 6327
- Other IDs
- 2014-002628-29, BH120771, 14/NE/1070, 2014
- Acronym
- CAPRI
- Status last verified
- Mar 2018
- First submitted
- 11 Mar 2015
- Last updated
- 29 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gatsiou A, Tual-Chalot S, Napoli M, Ortega-Gomez A, Regen T, Badolia R, Cesarini V, Garcia-Gonzalez C, Chevre R, Ciliberti G, Silvestre-Roig C, Martini M, Hoffmann J, Hamouche R, Visker JR, Diakos N, Wietelmann A, Silvestris DA, Georgiopoulos G, Moshfegh A, Schneider A, Chen W, Guenther S, Backs J, Kwak S, Selzman CH, Stamatelopoulos K, Rose-John S, Trautwein C, Spyridopoulos I, Braun T, Waisman A, Gallo A, Drakos SG, Dimmeler S, Sperandio M, Soehnlein O, Stellos K. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation. Immunity. 2023 May 9;56(5):979-997.e11. doi: 10.1016/j.immuni.2023.03.021. Epub 2023 Apr 25.
PubMed 37100060Cormack S, Mohammed A, Panahi P, Das R, Steel AJ, Chadwick T, Bryant A, Egred M, Stellos K, Spyridopoulos I; CAPRI investigators. Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction. Br J Clin Pharmacol. 2020 Jul;86(7):1387-1397. doi: 10.1111/bcp.14252. Epub 2020 Mar 11.
PubMed 32067256
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Effectiveness of Intravenous Ciclosporin on Reducing Reperfusion Injury in Patients Undergoing Primary Percutaneous Intervention: a Double-blind Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT02390674
- Acronym / sponsor ID
- CAPRI / R&D 6327
- Conditions
- Myocardial Reperfusion Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Newcastle University
- Study start
- Mar 2015
- Primary completion
- Apr 2017 (actual)
- Study completion
- 11 Nov 2017 (actual)
- First posted
- 17 Mar 2015 (estimated)
- 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.
Routine primary percutaneous coronary intervention (PPCI) for a heart attack involves opening a blocked artery with a balloon then inserting a metal scaffold (stent) to hold the artery open. During this procedure inflammation can occur causing further damage to the heart. The objective of this trial is to determine whether administration of the drug ciclosporin prior to PPCI reduces the amount of damage to the heart relative to treatment with placebo. The damage to the heart is assessed after 12 weeks by an magnetic resonance imaging (MRI) scan. Patients are followed-up after 12 months participation in the study.
This is a single centre study looking to recruit 68 patients.
Detailed description
Coronary heart disease is a condition in which the supply of blood and oxygen to the heart is reduced due to the narrowing of the arteries supplying the heart. A heart attack is caused when one of these arteries becomes blocked. Modern treatment for a heart attack is called primary percutaneous coronary intervention (PPCI). PPCI involves opening the blocked artery with a balloon and placing a stent (a small metal tube) in the artery to hold it open.
Research has shown that after opening the blocked artery, inflammation develops within the heart. This inflammation is generated by the immune system. Initial studies have suggested that certain immune system cells (T-cells) may be involved in causing much of the damage that occurs in the heart following a heart attack. The drug ciclosporin temporarily inhibits the immune system and it has been shown in a small number of patients that it reduces the size of the heart attack. The aim of this clinical trial is to investigate in a larger number of patients whether the size of the heart attack is reduced in patients treated with the drug ciclosporin prior to PPCI relative to patients treated with a placebo (saline).
To participate in the trial you must be having a large heart attack (STEMI - ST segment elevation myocardial infarction) and be undergoing a PPCI to unblock your artery. You must also be aged over 18 years. You will be randomised to receive either a single dose of the drug ciclosporin or placebo before your blocked artery is opened. Half the people will get the drug ciclosporin. This randomisation will enable us to compare the results to see whether treatment with ciclosporin reduces the size of the heart attack compared with placebo.
There may be no immediate benefit from taking part in the trial but the information we get from this trial will help improve the treatment of people having a heart attack in the future. As far as we know there are no disadvantages of taking part in the trial. If you are randomised to the 'drug' group, there is a very small risk of side effects from ciclosporin, such as high blood pressure and slight worsening of kidney function. We do not expect any side effects as the ciclosporin is only given once in the trial. On rare occasions allergic reactions have been observed. If any ciclosporin-related side effects were to occur, they would be expected soon after the drug was administered.
This is a single centre, randomised, double-blind, parallel group, placebo-controlled phase II/III trial comparing the efficacy of ciclosporin versus placebo in 68 patients with acute myocardial infarction undergoing PPCI. The trial is set in a tertiary care centre (Freeman Hospital, Newcastle upon Tyne, UK) and patients will be recruited over a period of 18 months. The trial is designed to show superiority regarding its primary endpoint. During initial hospitalisation following myocardial infarction, treatment is given once prior to performing the PPCI in the catheter laboratory. The duration of study for each patient is 12 months until final follow-up (12 weeks randomised controlled trial (RCT) followed by 9 months study follow-up). Should treatment with ciclosporin look promising, a larger trial will be designed to evaluate ciclosporin treatment fully. In contrast to the previous study, this trial is not restricted to anterior STEMI patients. It will also analyse changes in inflammatory response following reperfusion and will use MRI (current gold standard) in every patient to quantify infarct size, ejection fraction and microvascular obstruction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ciclosporin | Active comparator | Drug: CiclosporinSingle intravenous administration of ciclosporin (2.5mg per kilogram body weight) immediately prior to reperfusion during primary percutaneous coronary intervention. Ciclosporin is dissolved in saline (maximum concentration 2.5mg per millilitre) |
| Saline | Placebo comparator | Drug: SalineSingle intravenous administration of placebo (saline) immediately prior to reperfusion during primary percutaneous coronary intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients presenting with acute myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI)
- Age above 18 years
- Presenting within 6 hours of the onset chest pain and ST segment elevation. The culprit coronary artery has to be a major coronary artery with a diameter of at least 3mm and has to be proximally occluded (TIMI flow grade 0-1) at the time of admission coronary angiography
Key exclusion criteria (22 listed)
- Patients with any disorder associated with immunological dysfunction (acute or chronic inflammatory or neoplastic co-existing disease, known positive serology for HIV, or hepatitis)
- Clinically unstable patients (haemodynamically unstable, cardiogenic shock, unconscious patients)
- Patients with evidence of coronary collaterals to the infarct area
- Patients with an open (TIMI > 1) culprit coronary artery at the time of angiography.
- Previous myocardial infarction
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 |
|---|---|---|
| CiclosporinAlso: SandimmunComparison between ciclosporin and placebo | Drug | Ciclosporin |
| Saline | Drug | Saline |
Primary outcome
Change in infarct size
Time frame: 12 weeks after primary percutaneous coronary intervention (PPCI)
Change in infarct size 12 weeks post-PPCI as measured by cardiac MRI
3 secondary outcomes
Change in microvascular obstruction
Time frame: Measured once between day 2 and day 7 after PPCI
Change in salvage index
Time frame: Measured once between day 2 and day 7 after PPCI
Change in T lymphocyte count
Time frame: 5, 15, 30, 60 and 90 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
- Derived from this study: PubMed 37100060Gatsiou A, Tual-Chalot S, Napoli M, Ortega-Gomez A, Regen T, Badolia R, Cesarini V, Garcia-Gonzalez C, Chevre R, Ciliberti G, Silvestre-Roig C, Martini M, Hoffmann J, Hamouche R, Visker JR, Diakos N, Wietelmann A, Silvestris DA, Georgiopoulos G, Moshfegh A, Schneider A, Chen W, Guenther S, Backs J, Kwak S, Selzman CH, Stamatelopoulos K, Rose-John S, Trautwein C, Spyridopoulos I, Braun T, Waisman A, Gallo A, Drakos SG, Dimmeler S, Sperandio M, Soehnlein O, Stellos K. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation. Immunity. 2023 May 9;56(5):979-997.e11. doi: 10.1016/j.immuni.2023.03.021. Epub 2023 Apr 25.
- Derived from this study: PubMed 32067256Cormack S, Mohammed A, Panahi P, Das R, Steel AJ, Chadwick T, Bryant A, Egred M, Stellos K, Spyridopoulos I; CAPRI investigators. Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction. Br J Clin Pharmacol. 2020 Jul;86(7):1387-1397. doi: 10.1111/bcp.14252. Epub 2020 Mar 11.
Related trials for Myocardial Reperfusion Injury
RecruitingPhase 2
Prevention of Reperfusion Injury Outcomes Through Effective Cardioprotection Targeting Myocardial Infarction
Myocardial Infarction, Reperfusion Injury
Not yet recruitingPhase 2
Evaluating SGLT2 Inhibitors for the Reduction of No-Reflow Phenomenon in Patients Undergoing PCI
No Reflow Phenomenon, Reperfusion Injuries, Myocardial
RecruitingObservational study
Spectroscopic Assessment of Myocardial Oxygenation Changes in Pediatric Heart Surgery
Myocardial Ischemia, Heart Defects, Congenital
Active, not recruitingPhase 2
Effect of L-Carnitine on Biomarkers of Myocardial Reperfusion Injury in Patients With STEMI
Reperfusion Injury, Myocardial, Myocardial Infarction
Not yet recruitingPhase 2
Combined Antioxidant Therapy for Acute Myocardial Infarction
Acute Myocardial Infarction (AMI), ST Elevation (STEMI) Myocardial Infarction
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.
Ioakim Spyridopoulos, PhD, MD principal investigator
Newcastle University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ciclosporin and Saline in people with Myocardial Reperfusion Injury, run by Newcastle-upon-Tyne Hospitals NHS 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 3 inclusion and 22 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 29 Mar 2018. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in infarct size (time frame: 12 weeks after primary percutaneous coronary intervention (PPCI)). 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 NCT02390674, which also lists 2 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 29 Mar 2018.