Prevention of Left Ventricular Dysfunction During Chemotherapy

NCT ID: NCT01110824

Last Updated: 2013-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2012-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Myeloid Leukemia Precursor-cell Lymphoblastic Leukemia-Lymphoma Lymphoid Neoplasm Multiple Myeloma Lymphoma Autologous Hematopoietic Stem Cell Transplantation

Keywords

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Prevention ventricular dysfunction chemotherapy acute myeloid leukemia precursor-cell lymphoblastic leukemia multiple myeloma lymphoma ejection fraction Autologous hematopoietic stem cell transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Enalapril and carvedilol

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

Group Type EXPERIMENTAL

Enalapril and carvedilol

Intervention Type DRUG

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

Control

Control arm without intervention

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Enalapril and carvedilol

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

European Union

OTHER

Sponsor Role collaborator

Hospital Clinic of Barcelona

OTHER

Sponsor Role lead

Responsible Party

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Xavier Bosch

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xavier Bosch, M.D., PhD.

Role: STUDY_CHAIR

Hospital Clinic, University of Barcelona

Locations

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Hospital Clinic

Barcelona, Catalonia, Spain

Site Status

Hospital Clinic

Barcelona, Catalonia, Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 21807325 (View on PubMed)

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.

Reference Type RESULT
PMID: 23583763 (View on PubMed)

Other Identifiers

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2007-006604-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FIS EC07/90211

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OVERCOME

Identifier Type: -

Identifier Source: org_study_id