Prevention of Left Ventricular Dysfunction During Chemotherapy (OVERCOME)
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|ClinicalTrials.gov Identifier: NCT01110824|
Recruitment Status : Completed
First Posted : April 27, 2010
Last Update Posted : November 15, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Precursor-cell Lymphoblastic Leukemia-Lymphoma Lymphoid Neoplasm Multiple Myeloma Lymphoma Autologous Hematopoietic Stem Cell Transplantation||Drug: Enalapril and carvedilol||Phase 3|
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 (Clinical Trial)|
|Actual Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Prevention of Left Ventricular Dysfunction With Enalapril and Carvedilol in Patients Submitted to Intensive Chemotherapy for the Treatment of Malignant Hemopathies|
|Study Start Date :||April 2008|
|Actual Primary Completion Date :||December 2011|
|Actual Study Completion Date :||March 2012|
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
- 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 ]
- Incidence of death, heart failure or LV systolic disfunction (LVEF<45%) [ Time Frame: 6 months after randomization ]
- Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity [ Time Frame: Baseline ]
- Prognostic value for cardiac toxicity of troponin I and BNP [ Time Frame: up to 3 months ]
- Right and left ventricular volumes measured by CMR [ Time Frame: 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 ]
- 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 ]
- Serious adverse events [ Time Frame: 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01110824
|Barcelona, Catalunya, Spain, 08035|
|Barcelona, Catalunya, Spain, 08036|
|Study Chair:||Xavier Bosch, M.D., PhD.||Hospital Clinic, University of Barcelona|