Ciclosporin to reduce reperfusion injury in primary percutaneous coronary intervention

ISRCTN ISRCTN27767229
DOI https://doi.org/10.1186/ISRCTN27767229
EudraCT/CTIS number 2014-002628-29
ClinicalTrials.gov number NCT02390674
Secondary identifying numbers R&D 6327
Submission date
23/06/2015
Registration date
01/07/2015
Last edited
28/05/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
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 (blood vessels) supplying the heart. A heart attack is caused when one of these arteries becomes blocked. The 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 study 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 immediately before PPCI compared to patients treated with a dummy drug.

Who can participate?
To participate in the study you must be having a large heart attack (STEMI) and be undergoing a PPCI to unblock your artery. You must also be aged over 18.

What does the study involve?
You will be randomly allocated to receive either a single dose of the drug ciclosporin or a dummy drug before your blocked artery is opened. This will allow us to compare the results to see whether treatment with ciclosporin reduces the size of the heart attack compared with treatment with a dummy drug. You will need to come back to the hospital after 2 weeks for a blood test. After 3 months you will need to come back to the hospital for a heart magnetic resonance imaging (MRI) scan and a blood test. After 12 months you will have a telephone follow-up call.

What are the possible benefits and risks of participating?
There may be no immediate benefit from taking part in the study but the information we get 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 study. 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 study. 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 given.

Where is the study run from?
This study is run from the Freeman Hospital, Newcastle upon Tyne, UK.

When is the study starting and how long is it expected to run for?
The study started in March 2015 and it is aiming to recruit 68 patients over a period of 18 months. Each patient will be in the trial for 12 months.

Who is funding the study?
The study is being funded by the National Institute for Health Research Newcastle Biomedical Research Centre

Who is the main contact?
Alison J Steel, PhD
alison.steel@newcastle.ac.uk

Contact information

Dr Alison Steel
Public

Newcastle Clinical Trial Unit
1-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom

Prof Ioakim Spyridopoulos
Scientific

Institute of Genetic Medicine
International Centre for Life
Central Parkway
Newcastle upon Tyne
NE1 3BZ
United Kingdom

Study information

Study designInterventional single-centre double-blind randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titleEvaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention: a double-blind randomised controlled trial
Study acronymCAPRI
Study objectivesWhether an intravenous infusion of ciclosporin prior to reperfusion by coronary stenting will affect infarct size in patients with acute myocardial infarction.
Ethics approval(s)NRES Committee North East - Newcastle & North Tyneside 2, 24/07/2014, ref: 14/NE/1070
Health condition(s) or problem(s) studiedMyocardial reperfusion injury
InterventionActive comparator: single intravenous administration of ciclosporin (2.5 mg per kilogram body weight) immediately prior to reperfusion during primary percutaneous coronary intervention. Ciclosporin is dissolved in saline (maximum concentration 2.5 mg per millilitre)
Placebo comparator: single intravenous administration of saline immediately prior to reperfusion during primary percutaneous coronary intervention
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II/III
Drug / device / biological / vaccine name(s)Ciclosporin
Primary outcome measureInfarct size at 12 weeks post-PPCI as measured by cardiac magnetic resonance imaging (MRI).
Secondary outcome measures1. Microvascular obstruction after 2-7 days as measured by a single cardiac MRI scan
2. Salvage index after 2-7 days as measured by a single cardiac MRI scan
3. Change in T lymphocyte counts relative to baseline at 5, 15, 30, 60 and 90 minutes post-reperfusion
4. Number of clinical events (death, stroke or myocardial infarction) after 12 months
Overall study start date01/02/2014
Completion date15/09/2017

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants68
Total final enrolment52
Key inclusion criteria1. Patients presenting with acute myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (primary PCI)
2. Age above 18 years
3. 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 3 mm and has to be proximally occluded (TIMI flow grade 0-1) at the time of admission coronary angiography
Key exclusion criteria1. Patients with any disorder associated with immunological dysfunction (acute or chronic inflammatory or neoplastic co-existing disease, known positive serology for HIV, or hepatitis)
2. Clinically unstable patients (haemodynamically unstable, cardiogenic shock, unconscious patients)
3. Patients with evidence of coronary collaterals to the infarct area
4. Patients with an open (TIMI > 1) culprit coronary artery at the time of angiography
5. Previous myocardial infarction
6. Previous thrombolytic therapy
7. Patients with known hypersensitivity to ciclosporin or to egg, peanut or soya-bean proteins
8. Patients with known renal insufficiency (either known GFR <30 ml/min/1.73m2) or current medical care for severe renal insufficiency
9. Known liver insufficiency
10. Uncontrolled hypertension (>180/110 mmHg)
11. 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
12. 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 IMP administration)
13. Contraindication to cardiac MRI:
13.1. Pacemaker
13.2. Implantable defibrillator
14. Patients unable to undergo cardiac MRI for any of the following reasons:
14.1. 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
14.2. Claustrophobic - patients who cannot take elevators or who are afraid of narrow or enclosed spaces
14.3. Breathlessness - patients who suffer from breathlessness at rest or low exercise level (e.g. while walking on the level)
15. 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
16. Lack of capacity to give initial verbal consent
17. Life expectancy <1 year due to non-cardiac illness
Date of first enrolment16/03/2015
Date of final enrolment15/09/2017

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
United Kingdom

Sponsor information

The Newcastle upon Tyne Hospitals NHS Foundation Trust
Hospital/treatment centre

Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
England
United Kingdom

ROR logo "ROR" https://ror.org/05p40t847

Funders

Funder type

Government

NIHR Newcastle Biomedical Research Centre

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination plan
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results 28/05/2020 No No
HRA research summary 28/06/2023 No No

Editorial Notes

28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
16/04/2019: No publications found, verifying study status with principal investigator.