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

Phase 3
18 Years
70 Years
Open (Enrolling)
Acute Myeloid Leukemia, Precursor-cell Lymphoblastic Leukemia-Lymphoma, Lymphoid Neoplasm, Multiple Myeloma, Lymphoma, Autologous Hematopoietic Stem Cell Transplantation

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Trial Information

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

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 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

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

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.

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

- 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 ACEI,ARBs or beta-blockers

- Prior allergy to ACEI or ARBs

- Systolic blood pressure <90 mmHg

- Asthma

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

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

Outcome Time Frame:

6-9 months after randomization

Safety Issue:


Principal Investigator

Xavier Bosch, M.D., PhD.

Investigator Role:

Study Chair

Investigator Affiliation:

Hospital Clinic, University of Barcelona


Spain: Agencia EspaƱola de Medicamentos y Productos Sanitarios

Study ID:




Start Date:

April 2008

Completion Date:

December 2011

Related Keywords:

  • Acute Myeloid Leukemia
  • Precursor-cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoid Neoplasm
  • Multiple Myeloma
  • Lymphoma
  • Autologous Hematopoietic Stem Cell Transplantation
  • Prevention
  • ventricular dysfunction
  • chemotherapy
  • acute myeloid leukemia
  • precursor-cell lymphoblastic leukemia
  • multiple myeloma
  • lymphoma
  • ejection fraction
  • Autologous hematopoietic stem cell transplantation
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Ventricular Dysfunction, Left
  • Ventricular Dysfunction