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Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients (CIRCUS)

Primary Purpose

ST Elevation Acute Myocardial Infarction

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Injection of Cyclosporin
Placebo
Echocardiography
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ST Elevation Acute Myocardial Infarction focused on measuring STEMI, cyclosporine, reperfusion injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Eligibility criteria (for screening before hospital admission):

  1. All (male and female) patients, aged over 18, without any legal protection measure,
  2. Having a health coverage,
  3. Presenting within 12 hours of the onset of chest pain,
  4. Who have ST segment elevation ≥0.2 mV in two contiguous leads,
  5. For whom the clinical decision was made to treat with percutaneous coronary intervention (PCI).

    And (further inclusion criteria to be confirmed by the admission coronary-angiography):

  6. The culprit coronary artery has to be the LAD
  7. The LAD artery has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography.
  8. Preliminary oral informed consent followed by signed informed consent as soon as possible.

Patients undergoing either primary PCI or rescue PCI are eligible for the study. Patients with previous AMI, PCI or coronary artery bypass surgery (CABG) are eligible for the study.

Exclusion Criteria:

  1. Patients with loss of consciousness or confused
  2. Patients with cardiogenic shock
  3. Patients with the left circumflex or the right coronary artery (RCA) as the culprit artery, or with evidence of coronary collaterals to the risk region
  4. Patients with an opened (TIMI > 1) LAD coronary artery at admission on initial (admission) coronary angiography
  5. Patients with 5.2. known hypersensitivity to cyclosporine 5.3. known hypersensitivity to egg, peanut or Soya-bean proteins 5.4. known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency) 5.5. known liver insufficiency 5.6. uncontrolled (treated or untreated) hypertension (> 180/110 mmHg)
  6. Patients treated with any compound containing Hypericum perforatum (St.-John's-worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine
  7. Female patients currently pregnant or women of childbearing age who were not using contraception (oral diagnosis).
  8. Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation 8.2. cancer, lymphoma 8.3. known positive serology for HIV, or hepatitis

Sites / Locations

  • Algemeen Ziekenhuis Sint-Jan Brugge
  • Chu Charleroi
  • Hôpital universitaire d'Anvers (UZA)
  • CHU Mont-Godinne
  • Clinique ESQUIROL - SAINT-HILAIRE
  • Centre Hospitalier du Pays D'Aix
  • Centre Hospitalier Universitaire d'Angers
  • Centre Hospitalier d'Annecy
  • Hôpital Henri Duffaut
  • Clinique Lafourcade
  • Centre Hospitalier Universitaire
  • Hopital Louis Pradel, Hospices Civils de Lyon
  • CHRU- Hôpital de la Côte de Nacre
  • Centre Hospitalier General
  • CHU - Hôpital Gabriel Montpied
  • CH de Compiègne
  • CH Henri MONDOR
  • Hôpital du Bocage
  • Hôpital A. MICHALLON - CHU
  • Centre Hospitalier General
  • CHRU - Hôpital Cardiologique Calmette
  • Clinique de la Sauvegarde
  • Centre Hospitalier St Luc St Joseph
  • Institut Jacques Cartier
  • CHU Arnaud de Villeneuve
  • Clinique du Millénaire
  • CHU de Mulhouse
  • Clinique du Diaconat
  • Hôpital Guillaume et René Laennec
  • CHU de Nîmes
  • Polyclinique des Fleurs
  • APHP Hôpital Bichat
  • CH de Pau
  • Hôpital Haut Lévêque
  • Hôpital Claude Galien
  • Hôpital Pontchaillou
  • Hôpital Charles NICOLLE
  • Hôpitaux Universitaires, Nouvel Hôpital Civil
  • Clinique de l'Ormeau - CCV des Pyrénées
  • CHU de Rangueil
  • Clinique Saint Gatien
  • CHRU de Tours
  • Hôpital Brabois - CHU Nancy
  • Clinique du Tonkin
  • Hospital Universitari Vall d'Hebron

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cyclosporin

Control

Arm Description

Injection of Cyclosporin A : one single intravenous bolus injection of 2.5 mg/Kg Echocardiography

one single intravenous bolus injection of Placebo Echocardiography

Outcomes

Primary Outcome Measures

Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)]

Secondary Outcome Measures

Ejection fraction
Functional outcome
Left-Ventricular End-Diastolic Volume (LVEDV)
Functional outcome
Left-Ventricular End-Systolic Volume (LVESV)
Functional outcome
Total mortality
Cardiovascular death
Heart failure
In-hospital worsening of heart failure after reperfusion, or rehospitalization for: a)worsening of a heart failure existing at admission, b)appearance of "new" heart failure
Myocardial infarction
Unstable angina
Stroke
Infarct size
Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care
Infarct size: peak Troponin (T or I)
Explorative outcome. Cardiac prognostic factors.
Microvascular obstruction (no reflow)
Explorative outcome. Cardiac prognostic factors.

Full Information

First Posted
December 28, 2011
Last Updated
February 23, 2018
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT01502774
Brief Title
Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients
Acronym
CIRCUS
Official Title
Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Infarct size is a major determinant of prognosis after Acute Myocardial Infarction (AMI). The investigators recently reported that cyclosporine A, when administered immediately prior to percutaneous coronary intervention (PCI), can significantly reduce infarct size in STEMI (ST Elevation acute Myocardial Infarction) patients. The objective of the present study is to determine whether cyclosporine can improve STEMI patient clinical outcome. Nine-hundred and seventy two patients with ST elevation MI will be entered into a multicentre, randomized, placebo-controlled, double-blinded study. They will receive one single injection of cyclosporine A (CicloMulsion, verum) or an equivalent volume of placebo prior to reperfusion therapy by PCI. The incidence of the combined endpoint (mortality, hospitalization for heart failure, left ventricular (LV) remodeling) will be assessed at one year and three years after treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ST Elevation Acute Myocardial Infarction
Keywords
STEMI, cyclosporine, reperfusion injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
970 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cyclosporin
Arm Type
Experimental
Arm Description
Injection of Cyclosporin A : one single intravenous bolus injection of 2.5 mg/Kg Echocardiography
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
one single intravenous bolus injection of Placebo Echocardiography
Intervention Type
Drug
Intervention Name(s)
Injection of Cyclosporin
Other Intervention Name(s)
Cyclosporin A (CicloMulsion, verum)
Intervention Description
one single intravenous bolus injection of 2.5 mg/Kg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One single intravenous bolus injection of Placebo
Intervention Type
Procedure
Intervention Name(s)
Echocardiography
Intervention Description
1 year after AMI
Primary Outcome Measure Information:
Title
Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)]
Time Frame
at 1 year post-AMI
Secondary Outcome Measure Information:
Title
Ejection fraction
Description
Functional outcome
Time Frame
at 1 year
Title
Left-Ventricular End-Diastolic Volume (LVEDV)
Description
Functional outcome
Time Frame
at 1 year
Title
Left-Ventricular End-Systolic Volume (LVESV)
Description
Functional outcome
Time Frame
at 1 year
Title
Total mortality
Time Frame
at 1 year
Title
Cardiovascular death
Time Frame
at 1 year
Title
Heart failure
Description
In-hospital worsening of heart failure after reperfusion, or rehospitalization for: a)worsening of a heart failure existing at admission, b)appearance of "new" heart failure
Time Frame
at 1 year
Title
Myocardial infarction
Time Frame
at 1 year
Title
Unstable angina
Time Frame
at 1 year
Title
Stroke
Time Frame
at 1 year
Title
Infarct size
Description
Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care
Time Frame
at 1 year
Title
Infarct size: peak Troponin (T or I)
Description
Explorative outcome. Cardiac prognostic factors.
Time Frame
At admission and at 4 hours (+/- 30 minutes) after study treatment administration
Title
Microvascular obstruction (no reflow)
Description
Explorative outcome. Cardiac prognostic factors.
Time Frame
During hospitalization at admission

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eligibility criteria (for screening before hospital admission): All (male and female) patients, aged over 18, without any legal protection measure, Having a health coverage, Presenting within 12 hours of the onset of chest pain, Who have ST segment elevation ≥0.2 mV in two contiguous leads, For whom the clinical decision was made to treat with percutaneous coronary intervention (PCI). And (further inclusion criteria to be confirmed by the admission coronary-angiography): The culprit coronary artery has to be the LAD The LAD artery has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography. Preliminary oral informed consent followed by signed informed consent as soon as possible. Patients undergoing either primary PCI or rescue PCI are eligible for the study. Patients with previous AMI, PCI or coronary artery bypass surgery (CABG) are eligible for the study. Exclusion Criteria: Patients with loss of consciousness or confused Patients with cardiogenic shock Patients with the left circumflex or the right coronary artery (RCA) as the culprit artery, or with evidence of coronary collaterals to the risk region Patients with an opened (TIMI > 1) LAD coronary artery at admission on initial (admission) coronary angiography Patients with 5.2. known hypersensitivity to cyclosporine 5.3. known hypersensitivity to egg, peanut or Soya-bean proteins 5.4. known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency) 5.5. known liver insufficiency 5.6. uncontrolled (treated or untreated) hypertension (> 180/110 mmHg) Patients treated with any compound containing Hypericum perforatum (St.-John's-worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine Female patients currently pregnant or women of childbearing age who were not using contraception (oral diagnosis). Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation 8.2. cancer, lymphoma 8.3. known positive serology for HIV, or hepatitis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel OVIZE, MD, Prof
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Algemeen Ziekenhuis Sint-Jan Brugge
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Chu Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
Hôpital universitaire d'Anvers (UZA)
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
CHU Mont-Godinne
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Clinique ESQUIROL - SAINT-HILAIRE
City
Agen
ZIP/Postal Code
47000
Country
France
Facility Name
Centre Hospitalier du Pays D'Aix
City
Aix En Provence
ZIP/Postal Code
13616
Country
France
Facility Name
Centre Hospitalier Universitaire d'Angers
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
Centre Hospitalier d'Annecy
City
Annecy
ZIP/Postal Code
74011
Country
France
Facility Name
Hôpital Henri Duffaut
City
Avignon
ZIP/Postal Code
84000
Country
France
Facility Name
Clinique Lafourcade
City
Bayonne
ZIP/Postal Code
64100
Country
France
Facility Name
Centre Hospitalier Universitaire
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Hopital Louis Pradel, Hospices Civils de Lyon
City
Bron cedex
ZIP/Postal Code
69677
Country
France
Facility Name
CHRU- Hôpital de la Côte de Nacre
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Centre Hospitalier General
City
Chartres
ZIP/Postal Code
28018
Country
France
Facility Name
CHU - Hôpital Gabriel Montpied
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
CH de Compiègne
City
Compiegne
ZIP/Postal Code
60321
Country
France
Facility Name
CH Henri MONDOR
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hôpital du Bocage
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Hôpital A. MICHALLON - CHU
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Centre Hospitalier General
City
Hagueneau
ZIP/Postal Code
67504
Country
France
Facility Name
CHRU - Hôpital Cardiologique Calmette
City
Lille
Country
France
Facility Name
Clinique de la Sauvegarde
City
Lyon
ZIP/Postal Code
69009
Country
France
Facility Name
Centre Hospitalier St Luc St Joseph
City
Lyon
ZIP/Postal Code
69365
Country
France
Facility Name
Institut Jacques Cartier
City
Massy
ZIP/Postal Code
91300
Country
France
Facility Name
CHU Arnaud de Villeneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Clinique du Millénaire
City
Montpellier
ZIP/Postal Code
34960
Country
France
Facility Name
CHU de Mulhouse
City
Mulhouse
ZIP/Postal Code
68100
Country
France
Facility Name
Clinique du Diaconat
City
Mulhouse
ZIP/Postal Code
69607
Country
France
Facility Name
Hôpital Guillaume et René Laennec
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU de Nîmes
City
Nimes
ZIP/Postal Code
30029
Country
France
Facility Name
Polyclinique des Fleurs
City
Ollioules
ZIP/Postal Code
83192
Country
France
Facility Name
APHP Hôpital Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
CH de Pau
City
PAU
ZIP/Postal Code
64011
Country
France
Facility Name
Hôpital Haut Lévêque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Hôpital Claude Galien
City
Quincy Sous Senart
ZIP/Postal Code
91480
Country
France
Facility Name
Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35003
Country
France
Facility Name
Hôpital Charles NICOLLE
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Hôpitaux Universitaires, Nouvel Hôpital Civil
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Clinique de l'Ormeau - CCV des Pyrénées
City
Tarbes
ZIP/Postal Code
65000
Country
France
Facility Name
CHU de Rangueil
City
Toulouse
ZIP/Postal Code
31043
Country
France
Facility Name
Clinique Saint Gatien
City
Tours
ZIP/Postal Code
37042
Country
France
Facility Name
CHRU de Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Hôpital Brabois - CHU Nancy
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Clinique du Tonkin
City
Villeurbanne
ZIP/Postal Code
69100
Country
France
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
26321103
Citation
Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Rande JL, Unterseeh T, Le Breton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M. Cyclosporine before PCI in Patients with Acute Myocardial Infarction. N Engl J Med. 2015 Sep 10;373(11):1021-31. doi: 10.1056/NEJMoa1505489. Epub 2015 Aug 30.
Results Reference
background
PubMed Identifier
31832789
Citation
Bochaton T, Claeys MJ, Garcia-Dorado D, Mewton N, Bergerot C, Jossan C, Amaz C, Boussaha I, Thibault H, Ovize M. Importance of infarct size versus other variables for clinical outcomes after PPCI in STEMI patients. Basic Res Cardiol. 2019 Dec 12;115(1):4. doi: 10.1007/s00395-019-0764-8.
Results Reference
derived
PubMed Identifier
26027612
Citation
Mewton N, Cung TT, Morel O, Cayla G, Bonnefoy-Cudraz E, Rioufol G, Angoulvant D, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, Morice MC, Monassier JP, Ider O, Dubois-Rande JL, Unterseeh T, Lebreton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Hansson MJ, Elmer E, Boussaha I, Jossan C, Torner A, Claeys M, Garcia-Dorado D, Ovize M; CIRCUS Study Investigators. Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial). Am Heart J. 2015 Jun;169(6):758-766.e6. doi: 10.1016/j.ahj.2015.02.020. Epub 2015 Mar 13.
Results Reference
derived

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Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients

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