Prevention of Left Ventricular Dysfunction During Chemotherapy (OVERCOME)

Hospital Clinic of Barcelona

Status and phase

Completed

Phase 3

Conditions

Lymphoid Neoplasm

Multiple Myeloma

Lymphoma

Precursor-cell Lymphoblastic Leukemia-Lymphoma

Autologous Hematopoietic Stem Cell Transplantation

Acute Myeloid Leukemia

Treatments

Drug: Enalapril and carvedilol

Study type

Interventional

Funder types

Other

Identifiers

NCT01110824

FIS EC07/90211 (Other Grant/Funding Number)

OVERCOME

2007-006604-38 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

90 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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