Safety and Efficacy Study of TRO40303 for Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction

This study has been completed.
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Trophos
ClinicalTrials.gov Identifier:
NCT01374321
First received: June 14, 2011
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

Objectives of the phase 2 prospective, multicenter, randomized, double-blind, placebo-controlled study is to assess safety and efficacy of TRO40303 administered just before balloon inflation during percutaneous coronary intervention (PCI) for limitation of infarct size in patients treated for acute myocardial infarction (AMI).

The study is being conducted in 9 centres in Sweden, Denmark, Norway and France. One hundred eighty patients will be included. It will last one month per patient and its overall duration will be 11 months.

The efficacy will be assessed by infarct size expressed as area under the curve for creatine kinase and troponin I (blood sampling at D1, D2 and D3), and also evaluated by Cardiac Magnetic Resonance.

Safety will be assessed by

  • clinic evaluation,
  • blood samples (hematology, biochemistry, renal and hepatic function),
  • Recording and follow-up of major adverse events occurring during the first 48h after reperfusion (death, heart failure, AMI, stroke, recurrent ischemia, the need for repeat revascularization, renal or hepatic, vascular complication and bleeding).
  • ECG
  • Recording cardiac events during one month after AMI
  • Follow-up of global left ventricular function by Echocardiography at D3 and D30.

Demographic and medical history at inclusion and non-cardiac events occurring during the first 30 days will be recorded. TRO40303 plasma concentration will be assessed at 15 min, 6h, and 12h post the end of administration.

Sample size calculation assuming a reduction of 35% of the AUC for Troponin I release, for a statistical power of 85% and a probability of type I error of 0.05.

Main analysis: between-group comparisons of AUCs for serum troponin I and CK release will be performed using O'Brien's method for multiple endpoints testing.

Secondary analysis: comparisons of the CMR criteria described above will be performed using mixed model of ANCOVA.

All analyses will be performed on the Full Analysis Set and Per protocol populations.

Safety analysis: A comparison of the incidence of cumulative adverse clinical events between the groups will be performed by Fisher's exact tests.

Subjects will undergo primary PCI and receive concomitant medications according to current standard of care.

After coronary angiography is performed but just before balloon inflation is performed, patients who meet the enrollment criteria will be randomly assigned to either the control group or the TRO40303 group. Randomization is ensured by taking the treatment units in ascending and consecutive order in each strata (anterior/posterior as determined on ECG). Just before balloon inflation, ideally less than 5 minutes, and with a maximum of 15 minutes before balloon inflation and stenting, the patients in the TRO40303 group will receive an intravenous slow-bolus (35 mL/min) injection of 6 mg/kg of TRO40303 injected in peripheral IV. The patients in the control group will receive an equivalent volume of the placebo. Patients will be hospitalized for as long as there is a medical indication. CMR and echocardiography will accordingly be conducted as in/out patient between day 3 (ideally) and 5. A follow-up visit will be conducted one month after PCI.


Condition Intervention Phase
Acute Myocardial Infarctus
Drug: TRO40303
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase II, Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of TRO40303 for Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Trophos:

Primary Outcome Measures:
  • Infarct size expressed as area under the curve for Creatine kinase and Troponin I [ Time Frame: Blood samples will be collected at admission and every 6 hours until 72h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Infarct size evaluated by Cardiac Magnetic Resonance [ Time Frame: A cardiac magnetic resonance between day 3 and Day 5 after balloon inflation ] [ Designated as safety issue: No ]

Enrollment: 168
Study Start Date: October 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
single dose just before balloon inflation by slow bolus (35ml/min, peripheral IV)
Experimental: TRO40303 Drug: TRO40303
6 mg/kg, peripheral IV, single dose just before balloon inflation, slow bolus (35ml/min)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and Female with non childbearing potential patients
  2. Age > 18 years old
  3. First acute myocardial infarction
  4. Occlusion should affect the following coronary arteries: LAD,or the dominant or balanced RCA, or the dominant or balanced LCx
  5. Acute myocardial infarction defined as

    • nitrate resistant chest pain ≥ 30 min
    • ST elevation: New ST elevation at the J-point in two contiguous leads with the cut-off points: ≥ 2 mV in men or ≥ 0.15 mV in women in leads V2-V3 and/or ≥ O.1 mV in other leads
  6. Presenting within 6h of onset of chest pain
  7. Clinical decision to treat with percutaneous coronary intervention
  8. Occlusion of culprit artery with a Thrombolysis In Myocardial Infarction (TIMI) flow grade 0-1 at time of admission and before percutaneous coronary intervention
  9. Have signed an Informed Consent to participate to the trial before any study related procedure has been taken

Exclusion Criteria:

  1. Cardiac arrest, ventricular fibrillation, cardiogenic shock, stent thrombosis, previous AMI, angina within 48h before admission, previous CABG, treatment with intravenous fibrinolytic therapy within the 72 hours to PCI
  2. Atrial fibrillation (could confound CMR analysis)
  3. Pace-maker
  4. Concurrent inflammatory, infectious or malignant disease
  5. Biliary obstruction or hepatic insufficiency at the time of inclusion in the study
  6. Be possibly dependent on the Investigator or the Sponsor (eg including but not limited to affiliated employee)
  7. Participated in any other investigational drug or therapy study with a non-approved medication, within the previous 3 months
  8. Patient under guardianship
  9. History of egg allergy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01374321

Locations
Denmark
Aarhus University Hospital
Aalborg, Denmark, 9000
Odense University Hospital
Odense, Denmark, 5000
France
Hôpital Henri Mondor
Créteil, France, 94010
Hôpital Nord Marseille
Marseille, France
Hôpital La Timone
Marseille, France, 13005
Hôpital Européen Georges Pompidou
Paris, France, 75015
Norway
Haukeland University Hospital
Bergen, Norway, NO-5021
Oslo University Hospital
Oslo, Norway, 4956
Larsen
Stavanger, Norway, 4011
Sweden
Skane University Hospital
Lund, Sweden, SE-221 85
Karolinska University Hospital
Stockholm, Sweden, SE-171 76
Sponsors and Collaborators
Trophos
European Commission
Investigators
Principal Investigator: Dan Atar, Pr Oslo University Hospital Ulleval
  More Information

No publications provided

Responsible Party: Trophos
ClinicalTrials.gov Identifier: NCT01374321     History of Changes
Other Study ID Numbers: TRO40303CLEQ1491-1
Study First Received: June 14, 2011
Last Updated: November 21, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes
Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Norway: Norwegian Medicines Agency
Norway: Regional Ethics Commitee
Sweden: Medical Products Agency
Sweden: Ethics committee

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Reperfusion Injury
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on September 30, 2014