Coronary Artery Bypass SurgeryPhase 2Ciclo et CECNCT01002859
Effect of Preliminary Administration of Cyclosporine (Sandimmun ®) on Different Markers of Cardiac Ischaemia Induced by Cardiopulmonary Bypass
A Phase 2 study testing Sandimmum in people with Coronary Artery Bypass Surgery and Cardiopulmonary Bypass, run by University Hospital, Grenoble at 1 site in France.
Trial summary
Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Bypass Surgery, Cardiopulmonary Bypass
- What is being tested?
- Sandimmum
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2009to Jul 2011
- 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
- Patient hospitalized for a coronary artery bypass surgery
- Not urgent surgery
- Left ventricular ejection fraction (LVEF)> 40 %
- 18 years and older
- patient who have sign the informed consent form
- Affiliation to the French Social Security.
Who cannot join
- Beating heart surgery with or without Cardiopulmonary Bypass
- Patient receiving another surgical gesture combined to the CABG
- Myocardial infarction or vascular cerebral attack less than 30 days
- Previous History of cardiac surgery;
- Renal failure (creatinine > 200 µmol/l)
- Uncontrolled hypertension
Show all 17Show fewer
- hyperkaliemy;
- hyperuricemy;
- Acute Coronary Syndrome
- Malignant tumor
- Unchecked infection
- Previous intravenous administration of Sandimmun ®;
- allergy to ciclosporin, ethyl alcohol, castor oil or nitrogen
- Pregnant Woman, parturient without contraception, or breast-feeding
- Age < 18 years
- Patient who have not signed the form of consent;
- Patient Under guardianship or being the object of a legal protective measure
Trial locations and contacts
1 site in 1 country.
France1 site
Department of cardiac surgery - University Hospital of Grenoble
Grenoble, 38043
About this study
Official title: Double-Blind Phase II Pilot Monocentric Randomized Clinical Trial Evaluating the Effect of a Preliminary Administration of Cyclosporine on Different Markers of Cardiac Ischemia Led by the Aortic Cross-clamp During Coronary Artery Bypass Surgery With Cardiopulmonary Bypass.
Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass.
Read the detailed description
The coronary artery bypass surgery, in spite of substantial improvements during the last years, is still associated to a post-operative mortality and morbidity: myocardial infarction, heart failure, cardiac arrhythmia, renal failure, Stroke.
These complications are often due to ischaemia - reperfusion injury event. Recent studies showed that in case of cellular stress (in particular during the reperfusion after ischaemia) a not specific pore, called Mitochondrial permeability transition Pore (MPTP), could be opened. That caused the loss of ion homeostasis, then cell death as well as by apoptosis as by necrosis.
Prevent the opening of this MPTP during the myocardial reperfusion after coronary bypass, for example, is an important objective to improve the cardioprotection.
The Cyclosporin A, prevents the MPTP from opening. Several studies have shown an cytoprotection led by cyclosporin A, after ischaemia reperfusion in several models as isolated rats heart, in vivo rats heart and ex vivo myocardial ( atrial ) human tissues.
Recently, a multicentric study performed in humans, during the acute phase of myocardial infarction, showed a reduction of infarct size by approximately 40% in the cyclosporine group compared to control group.
- Being tested
- Sandimmum, Placebo
- Keywords
- Coronary artery bypass graft surgery (CABG), Cardiopulmonary Bypass (CPB), Cyclosporine, ischaemia reperfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SandimmumDrug
Intravenous injection of cyclosporine
PlaceboDrug
Intravenous Injection of NaCl solution
| Study group | Role | What they receive |
|---|---|---|
| cyclosporin | Active comparator | Intravenous cyclosporin injection. Receives: Drug: Sandimmum |
| Pacebo | Placebo comparator | Intravenous injection of NaCl solution. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass
Measured: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass.
Secondary outcomes (4)
Area under curve and maximal blood level of S100β protein
Measured: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass
Spontaneous defibrillation at aorta declamping; Post surgical atrial fibrillation; ECG (new Q wave); Transthoracic Echocardiogram (diastolic and systolic function study, research of paradoxical septal motion, study of cardiac output)....)
Measured: until Day 3 after the end of the cardiopulmonary bypass
Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level
Measured: until day 8 after the end of the cardiopulmonary bypass
Creatine blood levels
Measured: until 3 months after the end of the cardiopulmonary bypass
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2009 (estimated)
- Study startApr 2009
- Primary completionMay 2011
- Study completionJul 2011
Why it stopped: difficulties to include patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery Bypass SurgeryStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent BACH, MD, Principal investigator, Cardiac Surgery Department - University Hospital of Grenoble,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01002859
- Sponsor's protocol ID
- DCIC 08 04
- Acronym
- Ciclo et CEC
- Status last verified
- Sep 2014
- First submitted
- 26 Oct 2009
- Last updated
- 5 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999 Jul 15;341 ( Pt 2)(Pt 2):233-49.
PubMed 10393078Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection. Cardiovasc Res. 2004 Feb 15;61(3):372-85. doi: 10.1016/S0008-6363(03)00533-9.
PubMed 14962470Hausenloy DJ, Duchen MR, Yellon DM. Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res. 2003 Dec 1;60(3):617-25. doi: 10.1016/j.cardiores.2003.09.025.
PubMed 14659807Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM. Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H237-42. doi: 10.1152/ajpheart.01192.2004.
PubMed 15961375Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008 Jul 31;359(5):473-81. doi: 10.1056/NEJMoa071142.
PubMed 18669426
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Phase II Pilot Monocentric Randomized Clinical Trial Evaluating the Effect of a Preliminary Administration of Cyclosporine on Different Markers of Cardiac Ischemia Led by the Aortic Cross-clamp During Coronary Artery Bypass Surgery With Cardiopulmonary Bypass.
- ClinicalTrials.gov ID
- NCT01002859
- Acronym / sponsor ID
- Ciclo et CEC / DCIC 08 04
- Keywords
- Coronary artery bypass graft surgery (CABG), Cardiopulmonary Bypass (CPB), Cyclosporine, ischaemia reperfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficulties to include patients
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- May 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 27 Oct 2009 (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.
Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass.
Detailed description
The coronary artery bypass surgery, in spite of substantial improvements during the last years, is still associated to a post-operative mortality and morbidity: myocardial infarction, heart failure, cardiac arrhythmia, renal failure, Stroke.
These complications are often due to ischaemia - reperfusion injury event. Recent studies showed that in case of cellular stress (in particular during the reperfusion after ischaemia) a not specific pore, called Mitochondrial permeability transition Pore (MPTP), could be opened. That caused the loss of ion homeostasis, then cell death as well as by apoptosis as by necrosis.
Prevent the opening of this MPTP during the myocardial reperfusion after coronary bypass, for example, is an important objective to improve the cardioprotection.
The Cyclosporin A, prevents the MPTP from opening. Several studies have shown an cytoprotection led by cyclosporin A, after ischaemia reperfusion in several models as isolated rats heart, in vivo rats heart and ex vivo myocardial ( atrial ) human tissues.
Recently, a multicentric study performed in humans, during the acute phase of myocardial infarction, showed a reduction of infarct size by approximately 40% in the cyclosporine group compared to control group.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cyclosporin | Active comparator | Drug: SandimmumIntravenous cyclosporin injection. |
| Pacebo | Placebo comparator | Drug: PlaceboIntravenous injection of NaCl solution. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient hospitalized for a coronary artery bypass surgery
- Not urgent surgery
- Left ventricular ejection fraction (LVEF)> 40 %
- 18 years and older
- patient who have sign the informed consent form
Key exclusion criteria (17 listed)
- Beating heart surgery with or without Cardiopulmonary Bypass
- Patient receiving another surgical gesture combined to the CABG
- Myocardial infarction or vascular cerebral attack less than 30 days
- Previous History of cardiac surgery;
- Renal failure (creatinine > 200 µmol/l)
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 |
|---|---|---|
| SandimmumIntravenous injection of cyclosporine | Drug | cyclosporin |
| PlaceboIntravenous Injection of NaCl solution | Drug | Pacebo |
Primary outcome
Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass
Time frame: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass.
4 secondary outcomes
Area under curve and maximal blood level of S100β protein
Time frame: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass
Spontaneous defibrillation at aorta declamping; Post surgical atrial fibrillation; ECG (new Q wave); Transthoracic Echocardiogram (diastolic and systolic function study, research of paradoxical septal motion, study of cardiac output)....)
Time frame: until Day 3 after the end of the cardiopulmonary bypass
Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level
Time frame: until day 8 after the end of the cardiopulmonary bypass
Creatine blood levels
Time frame: until 3 months after the end of the cardiopulmonary bypass
Results and safety
The study was stopped early (reason given: difficulties to include patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2014.
- Background: PubMed 10393078Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999 Jul 15;341 ( Pt 2)(Pt 2):233-49.
- Background: PubMed 14962470Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection. Cardiovasc Res. 2004 Feb 15;61(3):372-85. doi: 10.1016/S0008-6363(03)00533-9.
- Background: PubMed 14659807Hausenloy DJ, Duchen MR, Yellon DM. Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res. 2003 Dec 1;60(3):617-25. doi: 10.1016/j.cardiores.2003.09.025.
- Background: PubMed 15961375Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM. Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H237-42. doi: 10.1152/ajpheart.01192.2004.
- Background: PubMed 18669426Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008 Jul 31;359(5):473-81. doi: 10.1056/NEJMoa071142.
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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.
Vincent BACH, MD principal investigator
Cardiac Surgery Department - University Hospital of Grenoble,
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 Sandimmum in people with Coronary Artery Bypass Surgery and Cardiopulmonary Bypass, run by University Hospital, Grenoble at 1 site in France.
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 17 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 5 Sep 2014. 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 France. 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: difficulties to include patients). 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?
Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass (time frame: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass.). 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 NCT01002859, which also lists 5 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 5 Sep 2014.