Prevention of Left Ventricular Dysfunction During Chemotherapy (OVERCOME)

November 14, 2013 updated by: Xavier Bosch, Hospital Clinic of Barcelona

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Hospital Clínic
      • Barcelona, Catalunya, Spain, 08036
        • Hospital Clínic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Congestive heart failure
  • LVEF<50%
  • Coronary artery disease,
  • significant valvulopathy or myocardiopathy
  • Renal failure (MDRD<30)
  • Liver failure
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Enalapril and carvedilol
Enalapril 2.5 to 10 mg BID plus Carvedilol 6.25 to 25 mg BID
Drug: Enalapril and carvedilol
Enalapril 2.5 to 10 mg BID Carvedilol 6.25 to 25 mg BID
No Intervention: Control
Control arm without intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
6 months after randomization

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of death, heart failure or LV systolic disfunction (LVEF<45%)
Time Frame: 6 months after randomization
6 months after randomization
Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity
Time Frame: Baseline
Baseline
Prognostic value for cardiac toxicity of troponin I and BNP
Time Frame: up to 3 months
up to 3 months
Right and left ventricular volumes measured by CMR
Time Frame: 6 months after randomization
6 months after randomization
Subgroup analysis by diagnosis (acute leukemia vs. other malignant hemopathies submitted to autologous peripheral blood stem cell transplantation), and positive biomarkers (TnI, BNP).
Time Frame: 6 months after randomization
6 months after randomization
Incidence of an absolute decrease in LVEF>10 percent units associated with a decline below its normal limit of 50%
Time Frame: 6 months after randomization
6 months after randomization
Serious adverse events
Time Frame: 6 months after randomization
6 months after randomization
the incidence of LV dysfunction as assessed by the measurement of the LV strain, and of diastolic dysfunction measured by echo-Doppler
Time Frame: 6 months after randomization
6 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Clinic of Barcelona

Collaborators

Instituto de Salud Carlos III
European Union

Investigators

  • Study Chair: Xavier Bosch, M.D., PhD., Hospital Clinic, University of Barcelona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

April 23, 2010

First Submitted That Met QC Criteria

April 23, 2010

First Posted (Estimate)

April 27, 2010

Study Record Updates

Last Update Posted (Estimate)

November 15, 2013

Last Update Submitted That Met QC Criteria

November 14, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OVERCOME
  • 2007-006604-38 (EudraCT Number)
  • FIS EC07/90211 (Other Grant/Funding Number: ISCIII)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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