Acute Myocardial InfarctusPhase 2NCT01374321
Safety and Efficacy Study of TRO40303 for Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction
A Phase 2 study testing TRO40303 in people with Acute Myocardial Infarctus, run by Hoffmann-La Roche at 11 sites in 4 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myocardial Infarctus
- What is being tested?
- TRO40303
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- 11 sitesin 4 countries
- Study dates
- Oct 2011to Sep 2013
- 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
- Male and Female with non childbearing potential patients
- Age > 18 years old
- First acute myocardial infarction
- Occlusion should affect the following coronary arteries: LAD,or the dominant or balanced RCA, or the dominant or balanced LCx
- Acute myocardial infarction defined as
- nitrate resistant chest pain ≥ 30 min
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- 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
- Presenting within 6h of onset of chest pain
- Clinical decision to treat with percutaneous coronary intervention
- Occlusion of culprit artery with a Thrombolysis In Myocardial Infarction (TIMI) flow grade 0-1 at time of admission and before percutaneous coronary intervention
- Have signed an Informed Consent to participate to the trial before any study related procedure has been taken
Who cannot join
- 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
- Atrial fibrillation (could confound CMR analysis)
- Pace-maker
- Concurrent inflammatory, infectious or malignant disease
- Biliary obstruction or hepatic insufficiency at the time of inclusion in the study
- Be possibly dependent on the Investigator or the Sponsor (eg including but not limited to affiliated employee)
Show all 9Show fewer
- Participated in any other investigational drug or therapy study with a non-approved medication, within the previous 3 months
- Patient under guardianship
- History of egg allergy
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
France4 sites
Hôpital Henri Mondor
Créteil, 94010
Hôpital La Timone
Marseille, 13005
Hôpital Nord Marseille
Marseille
Hôpital Européen Georges Pompidou
Paris, 75015
Norway3 sites
Haukeland University Hospital
Bergen, NO-5021
Oslo University Hospital
Oslo, 4956
Larsen
Stavanger, 4011
Denmark2 sites
Aarhus University Hospital
Aalborg, 9000
Odense University Hospital
Odense, 5000
Sweden2 sites
Skane University Hospital
Lund, SE-221 85
Karolinska University Hospital
Stockholm, SE-171 76
About this study
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
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.
Read more
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.
- Conditions
- Acute Myocardial Infarctus
- Being tested
- TRO40303, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRO40303Drug
6 mg/kg, peripheral IV, single dose just before balloon inflation, slow bolus (35ml/min)
PlaceboDrug
single dose just before balloon inflation by slow bolus (35ml/min, peripheral IV)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| TRO40303 | Experimental | Not described Receives: Drug: TRO40303 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infarct size expressed as area under the curve for Creatine kinase and Troponin I
Measured: Blood samples will be collected at admission and every 6 hours until 72h
Secondary outcomes (1)
Infarct size evaluated by Cardiac Magnetic Resonance
Measured: A cardiac magnetic resonance between day 3 and Day 5 after balloon inflation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2011 (estimated)
- Study startOct 2011
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Myocardial InfarctusStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Dan Atar, Pr, Principal investigator, Ullevaal University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01374321
- Sponsor's protocol ID
- TRO40303CLEQ1491-1
- Status last verified
- Jul 2018
- First submitted
- 14 Jun 2011
- Last updated
- 1 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nordlund D, Heiberg E, Carlsson M, Frund ET, Hoffmann P, Koul S, Atar D, Aletras AH, Erlinge D, Engblom H, Arheden H. Extent of Myocardium at Risk for Left Anterior Descending Artery, Right Coronary Artery, and Left Circumflex Artery Occlusion Depicted by Contrast-Enhanced Steady State Free Precession and T2-Weighted Short Tau Inversion Recovery Magnetic Resonance Imaging. Circ Cardiovasc Imaging. 2016 Jul;9(7):e004376. doi: 10.1161/CIRCIMAGING.115.004376.
PubMed 27412659Engblom H, Tufvesson J, Jablonowski R, Carlsson M, Aletras AH, Hoffmann P, Jacquier A, Kober F, Metzler B, Erlinge D, Atar D, Arheden H, Heiberg E. A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data. J Cardiovasc Magn Reson. 2016 May 4;18(1):27. doi: 10.1186/s12968-016-0242-5.
PubMed 27145749Tufvesson J, Carlsson M, Aletras AH, Engblom H, Deux JF, Koul S, Sorensson P, Pernow J, Atar D, Erlinge D, Arheden H, Heiberg E. Automatic segmentation of myocardium at risk from contrast enhanced SSFP CMR: validation against expert readers and SPECT. BMC Med Imaging. 2016 Mar 5;16:19. doi: 10.1186/s12880-016-0124-1.
PubMed 26946139
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01374321
- Acronym / sponsor ID
- TRO40303CLEQ1491-1
- Conditions
- Acute Myocardial Infarctus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- European Commission
- Study start
- Oct 2011
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 15 Jun 2011 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| TRO40303 | Experimental | Drug: TRO40303 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and Female with non childbearing potential patients
- Age > 18 years old
- First acute myocardial infarction
- Occlusion should affect the following coronary arteries: LAD,or the dominant or balanced RCA, or the dominant or balanced LCx
- Acute myocardial infarction defined as
Key exclusion criteria (9 listed)
- 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
- Atrial fibrillation (could confound CMR analysis)
- Pace-maker
- Concurrent inflammatory, infectious or malignant disease
- Biliary obstruction or hepatic insufficiency at the time of inclusion in the study
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 |
|---|---|---|
| TRO403036 mg/kg, peripheral IV, single dose just before balloon inflation, slow bolus (35ml/min) | Drug | TRO40303 |
| Placebosingle dose just before balloon inflation by slow bolus (35ml/min, peripheral IV) | Drug | Placebo |
Primary outcome
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
1 secondary outcome
Infarct size evaluated by Cardiac Magnetic Resonance
Time frame: A cardiac magnetic resonance between day 3 and Day 5 after balloon inflation
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 1 Aug 2018.
- Derived from this study: PubMed 27412659Nordlund D, Heiberg E, Carlsson M, Frund ET, Hoffmann P, Koul S, Atar D, Aletras AH, Erlinge D, Engblom H, Arheden H. Extent of Myocardium at Risk for Left Anterior Descending Artery, Right Coronary Artery, and Left Circumflex Artery Occlusion Depicted by Contrast-Enhanced Steady State Free Precession and T2-Weighted Short Tau Inversion Recovery Magnetic Resonance Imaging. Circ Cardiovasc Imaging. 2016 Jul;9(7):e004376. doi: 10.1161/CIRCIMAGING.115.004376.
- Derived from this study: PubMed 27145749Engblom H, Tufvesson J, Jablonowski R, Carlsson M, Aletras AH, Hoffmann P, Jacquier A, Kober F, Metzler B, Erlinge D, Atar D, Arheden H, Heiberg E. A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data. J Cardiovasc Magn Reson. 2016 May 4;18(1):27. doi: 10.1186/s12968-016-0242-5.
- Derived from this study: PubMed 26946139Tufvesson J, Carlsson M, Aletras AH, Engblom H, Deux JF, Koul S, Sorensson P, Pernow J, Atar D, Erlinge D, Arheden H, Heiberg E. Automatic segmentation of myocardium at risk from contrast enhanced SSFP CMR: validation against expert readers and SPECT. BMC Med Imaging. 2016 Mar 5;16:19. doi: 10.1186/s12880-016-0124-1.
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.
Dan Atar, Pr principal investigator
Ullevaal University Hospital
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TRO40303 in people with Acute Myocardial Infarctus, run by Hoffmann-La Roche at 11 sites in 4 countries.
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 11 inclusion and 9 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 1 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France, Norway, Denmark, Sweden. 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?
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). 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 NCT01374321, which also lists 3 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 1 Aug 2018.