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ST Elevation Acute Myocardial InfarctionPhase 3COMBAT-MINCT02404376

COMBinAtion Therapy in Myocardial Infarction: The COMBAT-MI Trial

A Phase 3 study testing Exenatide and Remote Ischemic Conditioning (RIC) in people with ST Elevation Acute Myocardial Infarction, run by Hospital Universitari Vall d'Hebron Research Institute at 6 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Remote ischemic conditioning (RIC) and intravenous exenatide administered immediately before primary angioplasty have been found to limit infarct size in patients with STEMI (ST segment elevation myocardial infarction), but the reduction is limited. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ST Elevation Acute Myocardial Infarction
What is being tested?
Exenatide and Remote Ischemic Conditioning (RIC)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
378 participants
Where
6 sitesSpain
Study dates
Mar 2016to Jun 2020
Phase
Phase 3
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

  • Men or women ≥18 years of age
  • STEMI characterized by 2 mm ST segment elevation in 2 or more V1 through V4 leads or presumed new left bundle branch block with minimum of 1 mm concordant ST elevation or 1 mV(millivolt) ST segment elevation in the limb leads (II, III and aVF leads, I, aVL leads) and V4-V6.
  • Patients presenting within 6 hours of chest pain.

Who cannot join

  • Known hypersensitivity to exenatide or any of the excipients
  • Known contraindication to CMR imaging such as significant claustrophobia, severe allergy to gadolinium chelate contrast, severe renal insufficiency (defined as estimated glomerular filtration rate [eGFR] (epidermal growth factor receptor) <30 mL/min/1.73 m2), presence of CMRI contraindicated implanted devices (e.g., pacemaker, implanted cardiac defibrillator, cardiac resynchronization therapy device, cochlear implant), embedded metal objects (e.g., shrapnel), or any other contraindication for CMRI.
  • Assumed life expectancy < 1 year e.g. due to non-cardiac disease.
  • TIMI flow grade > 1 at the time of diagnostic coronary angiography. These patients will be excluded from the analysis of infarct size but will be included in the safety analysis.
  • Pregnant women
  • Patients with loss of consciousness or confused, not able to read the information and to sign the writting consent
  • Patients with oro-tracheal intubation
  • Patients with cardiogenic shock persisting 48h after reperfusion

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Spain6 sites
  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitario Valle de Hebron

    Barcelona, 08035

  • Hospital Universitario Arnau de Vilanova

    Lleida, 25198

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Clínico Universitario de Santiago de Compostela

    Santiago de Compostela, La Coruña, 15706

  • Hospital Universitari de Tarragona Joan 23

    Tarragona, 43005

Other trials in Spain

About this study

Remote ischemic conditioning (RIC) and intravenous exenatide administered immediately before primary angioplasty have been found to limit infarct size in patients with STEMI (ST segment elevation myocardial infarction), but the reduction is limited. This study investigates whether a combination therapy including both therapies is more effective.

Read the detailed description

COMBAT-MI is an investigator-driven, randomized, double-blind and placebo-controlled clinical trial aimed at evaluating the effect of Remote Ischemic Conditioning and exenatide, alone and in combination, on Myocardial Infarct size in 428 STEMI patients (107 per group) (ST segment elevation myocardial infarction). Patients with TIMI (Thrombolysis in Myocardial Infarction) flow grade > 1 will be excluded. The study has a 2 x 2 factorial design (Remote Ischemic Conditioning , Exenatide, both or neither). The primary end-point will be Myocardial Infarct size measured by Cardiac Magnetic Resonance Imaging (CMRI) performed 3 - 7 days after primary Percutaneous Coronary Intervention (pPCI) (expressed as % of left ventricular (LV) mass). Sample size has been calculated in 274 patients with TIMI 0-1 available for analysis of the primary end-point, and inclusion will end when this number is reached, which will require, according to the current rate of TIMI 0-1 in our STEMI population, to randomize 428 patients. Secondary end-points will include myocardial salvage index, based on angiographic and CMRI derived estimations of the area at risk, and frequency of Major Adverse Cardiovascular Events (MACE) and of major adverse events during admission.

Being tested
Exenatide, Remote Ischemic Conditioning (RIC), Placebo
Keywords
STEMI, Reperfusion Injury, Myocardial Infarction, Myocardial Ischemia, Remote Ischemic Conditioning, Exenatide, Glucagon-Like Peptide-1 (GLP-1), Acute Coronary Syndrome, Cardioprotection
Medical subject headings
ST Elevation Myocardial Infarction, Reperfusion Injury, Myocardial Infarction, Myocardial Ischemia, Acute Coronary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ExenatideDrug

    Intravenous administration of Exenatide

  • Remote Ischemic Conditioning (RIC)Other

    Remote ischemic conditioning with a cuff in the arm

  • PlaceboDrug

    Intrevenous administration of Placebo

Study groups in NCT02404376
Study groupRoleWhat they receive
Remote Ischemic ConditioningActive comparatorRemote Ischemic Conditioning + placebo
Receives: Other: Remote Ischemic Conditioning (RIC); Drug: Placebo
Combined treatmentActive comparatorRemote Ischemic Conditioning + exenatide
Receives: Drug: Exenatide; Other: Remote Ischemic Conditioning (RIC)
PlaceboPlacebo comparatorSham Remote Ischemic Conditioning + placebo
Receives: Other: Remote Ischemic Conditioning (RIC); Drug: Placebo
ExenatideActive comparatorSham Remote Ischemic Conditioning + exenatide
Receives: Drug: Exenatide; Other: Remote Ischemic Conditioning (RIC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Myocardial Infarct Size

    MI, measured by late gadolinium enhancement in CMRI 3-7 days after pPCI, and expressed as percent of left ventricular mass.

    Measured: 3-7 days after pPCI

Secondary outcomes (6)
  1. Myocardial salvage index

    Myocardial salvage index defined as the difference between infarct size and area at risk, defined by the T2 CMRI and expressed as a percent of total LV (Left Ventricular) mass, divided by the area at risk.

    Measured: 3-7 days after pPCI

  2. Transmurality index

    Transmurality index, defined as the ratio of the mass of myocardium showing late gadolinium enhancement to the mass of the myocardial segment containing it.

    Measured: 3-7 days after pPCI

  3. Ventricular volumes

    LV (Left Ventricular) end-diastolic volume and LVEF (Left Ventricular Ejection Fraction), as determined by CMRI.

    Measured: 3-7 days after pPCI

  4. Microvascular obstruction

    Volume of myocardium with microvascular obstruction determined by late gadolinium enhancement expressed as percent of infarct size.

    Measured: 3-7 days after pPCI

  5. Markers of successful reperfusion

    Markers of successful myocardial reperfusion: ST segment resolution 90 minutes post-pPCI , TIMI flow and frame-count post-pPCI , and TIMI blush grade .

    Measured: First 90 min after reperfusion

  6. Major adverse cardiac events (MACE)

    MACE rate during hospitalization, defined as death, non-fatal myocardial rupture, or appearance or worsening of heart failure during the hospitalization period and after 1 year of follow-up

    Measured: Hospital discharge and expected average of 1 week, one year follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2015 (estimated)
  2. Study startMar 2016
  3. Primary completionAug 2019
  4. Study completionJun 2020

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
378 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02404376
Sponsor's protocol ID
COMBAT-MI
Acronym
COMBAT-MI
Status last verified
Feb 2020
First submitted
20 Mar 2015
Last updated
3 Nov 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, Jorgensen E, Helqvist S, Saunamaki K, Clemmensen P, Holmvang L, Thuesen L, Krusell LR, Jensen JS, Kober L, Treiman M, Holst JJ, Engstrom T. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012 Jun;33(12):1491-9. doi: 10.1093/eurheartj/ehr309. Epub 2011 Sep 14.

    PubMed 21920963
  • Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010 Feb 27;375(9716):727-34. doi: 10.1016/S0140-6736(09)62001-8.

    PubMed 20189026
  • White SK, Frohlich GM, Sado DM, Maestrini V, Fontana M, Treibel TA, Tehrani S, Flett AS, Meier P, Ariti C, Davies JR, Moon JC, Yellon DM, Hausenloy DJ. Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2015 Jan;8(1 Pt B):178-188. doi: 10.1016/j.jcin.2014.05.015. Epub 2014 Sep 17.

    PubMed 25240548
  • Garcia-Dorado D, Garcia-del-Blanco B, Otaegui I, Rodriguez-Palomares J, Pineda V, Gimeno F, Ruiz-Salmeron R, Elizaga J, Evangelista A, Fernandez-Aviles F, San-Roman A, Ferreira-Gonzalez I. Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: a randomized controlled clinical trial. Int J Cardiol. 2014 Dec 20;177(3):935-41. doi: 10.1016/j.ijcard.2014.09.203. Epub 2014 Oct 7.

    PubMed 25449504
  • Consegal M, Barba I, Garcia Del Blanco B, Otaegui I, Rodriguez-Palomares JF, Marti G, Serra B, Bellera N, Ojeda-Ramos M, Valente F, Carmona MA, Miro-Casas E, Sambola A, Lidon RM, Baneras J, Barrabes JA, Rodriguez C, Benito B, Ruiz-Meana M, Inserte J, Ferreira-Gonzalez I, Rodriguez-Sinovas A. Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk. Sci Rep. 2023 Apr 27;13(1):6907. doi: 10.1038/s41598-023-34196-7.

    PubMed 37106099

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Exenatide and Remote Ischemic Conditioning (RIC) in people with ST Elevation Acute Myocardial Infarction, run by Hospital Universitari Vall d'Hebron Research Institute at 6 sites in Spain.

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 3 inclusion and 8 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 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Myocardial Infarct Size (time frame: 3-7 days after pPCI). 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 NCT02404376, 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 3 Nov 2020.

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