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Acute Myeloid LeukemiaPhase 3OVERCOMENCT01110824

Prevention of Left Ventricular Dysfunction During Chemotherapy

A Phase 3 study testing Enalapril and carvedilol in people with Acute Myeloid Leukemia and Precursor-cell Lymphoblastic Leukemia-Lymphoma, run by Hospital Clinic of Barcelona at 2 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

The investigators' objective is to assess the efficacy of the combined treatment with enalapril and carvedilol in the prevention of left ventricular systolic dysfunction in patients with hematological malignancies submitted to intensive chemotherapy with potential cardiotoxicity. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Enalapril and carvedilol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
2 sitesSpain
Study dates
Apr 2008to Mar 2012
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patients 18-70 years old
  • Sinus rhythm
  • Normal LVEF (>=50%)
  • Patients recently diagnosed of acute leukemia to be submitted to intensive chemotherapy or
  • Patients with other hemopathies submitted to autologous peripheral blood stem cell transplantation
  • Signed informed consent

Who cannot join

  • Congestive heart failure
  • LVEF<50%
  • Coronary artery disease,
  • significant valvulopathy or myocardiopathy
  • Renal failure (MDRD<30)
  • Liver failure
Show all 15Show fewer
  • Ongoing or expected need to be treated with angiotensin-converting enzyme inhibitors (ACE-i),angiotensin II receptor blockers (ARB) or beta-blockers
  • Prior allergy to ACEI or ARB
  • Systolic blood pressure <90 mmHg
  • Asthma
  • Auriculoventricular (AV) block or sinus bradycardia (HR<60 bpm)
  • Persistent atrial fibrillation
  • Need to be treated with Class I antiarrhythmic drugs
  • Pregnancy
  • Inability or unwillingness to give unformed consent

Trial locations and contacts

2 sites in 1 country.

Spain2 sites

  • Hospital Clinic

    Barcelona, Catalonia, 08035

  • Hospital Clinic

    Barcelona, Catalonia, 08036

Other trials in Spain

About this study

Official title: Prevention of Left Ventricular Dysfunction With Enalapril and Carvedilol in Patients Submitted to Intensive Chemotherapy for the Treatment of Malignant Hemopathies

The investigators' objective is to assess the efficacy of the combined treatment with enalapril and carvedilol in the prevention of left ventricular systolic dysfunction in patients with hematological malignancies submitted to intensive chemotherapy with potential cardiotoxicity.

The hypothesis is that these drugs administered during chemotherapy may prevent left ventricular systolic dysfunction.

Read the detailed description

The prognosis of patients with hematological malignancies has greatly improved in the last years with the use of new chemotherapeutic drugs and regimens at the cost of significant adverse events such as cardiac toxicity. Asymptomatic left ventricular systolic dysfunction limits the specific treatment of the patients and their long-term survival, since a significant proportion of them will relapse within 5 years after front-line therapy and will require further salvage treatment, including hematopoietic stem-cell transplantation in most instances.

Angiotensin-converting enzyme inhibitors (ACEIs) have showed to have preventive effects against chemotherapy-induced cardiotoxicity in animal models, and in patients with early cardiotoxicity. Carvedilol prevent free radical release, mitochondrial dysfunction, apoptosis, and dilated cardiomyopathy in animals treated with anthracyclines, and have shown promising results in preventing chemotherapy-induced left ventricular dysfunction in patients.

As demonstrated in post-infarction patients, the combined treatment with an ACEI and carvedilol could have additive effects to prevent LV dysfunction in patients with hematological malignancies at high risk of cardiac toxicity. Therefore, we designed the OVERCOME (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies) study, a prospective, randomized trial to evaluate the combined effect of enalapril and carvedilol on the prevention of left ventricular dysfunction in patients with malignant hemopathies undergoing intensive chemotherapy.

Being tested
Enalapril and carvedilol
Keywords
Prevention, ventricular dysfunction, chemotherapy, acute myeloid leukemia, precursor-cell lymphoblastic leukemia, multiple myeloma, lymphoma, ejection fraction, Autologous hematopoietic stem cell transplantation
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Multiple Myeloma, Lymphoma, Ventricular Dysfunction

What participants receive

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

  • Enalapril and carvedilolDrug

    Enalapril 2.5 to 10 mg BID Carvedilol 6.25 to 25 mg BID

Study groups in NCT01110824
Study groupRoleWhat they receive
Enalapril and carvedilolExperimentalEnalapril 2.5 to 10 mg BID plus Carvedilol 6.25 to 25 mg BID
Receives: Drug: Enalapril and carvedilol
ControlNo interventionControl arm without intervention

What is being measured

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

  1. Change from baseline in left ventricular ejection fraction (LVEF) measured by echocardiography and by cardiac magnetic resonance imaging (CMR).

    Measured: 6 months after randomization

Secondary outcomes (8)

  1. Incidence of death, heart failure or LV systolic disfunction (LVEF<45%)

    Measured: 6 months after randomization

  2. Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity

    Measured: Baseline

  3. Prognostic value for cardiac toxicity of troponin I and BNP

    Measured: up to 3 months

  4. Right and left ventricular volumes measured by CMR

    Measured: 6 months after randomization

  5. Subgroup analysis by diagnosis (acute leukemia vs. other malignant hemopathies submitted to autologous peripheral blood stem cell transplantation), and positive biomarkers (TnI, BNP).

    Measured: 6 months after randomization

  6. Incidence of an absolute decrease in LVEF>10 percent units associated with a decline below its normal limit of 50%

    Measured: 6 months after randomization

  7. Serious adverse events

    Measured: 6 months after randomization

  8. the incidence of LV dysfunction as assessed by the measurement of the LV strain, and of diastolic dysfunction measured by echo-Doppler

    Measured: 6 months after randomization

Timeline

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

  1. First posted27 Apr 2010 (estimated)
  2. Study startApr 2008
  3. Primary completionDec 2011
  4. Study completionMar 2012

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01110824
Sponsor's protocol ID
OVERCOME
Other IDs
2007-006604-38, FIS EC07/90211
Acronym
OVERCOME
Status last verified
Nov 2013
First submitted
23 Apr 2010
Last updated
15 Nov 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Bosch X, Esteve J, Sitges M, de Caralt TM, Domenech A, Ortiz JT, Monzo M, Morales-Ruiz M, Perea RJ, Rovira M. Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial. J Card Fail. 2011 Aug;17(8):643-8. doi: 10.1016/j.cardfail.2011.03.008. Epub 2011 May 6.

    PubMed 21807325

  • Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, Morales-Ruiz M, Perea RJ, Monzo M, Esteve J. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013 Jun 11;61(23):2355-62. doi: 10.1016/j.jacc.2013.02.072. Epub 2013 Apr 10.

    PubMed 23583763

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enalapril and carvedilol in people with Acute Myeloid Leukemia and Precursor-cell Lymphoblastic Leukemia-Lymphoma, run by Hospital Clinic of Barcelona at 2 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 6 inclusion and 15 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 15 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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. 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?

Change from baseline in left ventricular ejection fraction (LVEF) measured by echocardiography and by cardiac magnetic resonance imaging (CMR). (time frame: 6 months after randomization). 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 NCT01110824, which also lists 2 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 15 Nov 2013.

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