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Prevention of Left Ventricular Dysfunction During Chemotherapy (OVERCOME)

This study has been completed.
Sponsor:
Collaborators:
Instituto de Salud Carlos III
European Union
Information provided by (Responsible Party):
Xavier Bosch, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT01110824
First received: April 23, 2010
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prevention of Left Ventricular Dysfunction With Enalapril and Carvedilol in Patients Submitted to Intensive Chemotherapy for the Treatment of Malignant Hemopathies

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of death, heart failure or LV systolic disfunction (LVEF<45%) [ Time Frame: 6 months after randomization ] [ Designated as safety issue: No ]
  • Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Prognostic value for cardiac toxicity of troponin I and BNP [ Time Frame: up to 3 months ] [ Designated as safety issue: No ]
  • Right and left ventricular volumes measured by CMR [ Time Frame: 6 months after randomization ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Serious adverse events [ Time Frame: 6 months after randomization ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: April 2008
Study Completion Date: March 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110824

Locations
Spain
Hospital Clinic
Barcelona, Catalunya, Spain, 08036
Hospital Clinic
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Hospital Clinic of Barcelona
Instituto de Salud Carlos III
European Union
Investigators
Study Chair: Xavier Bosch, M.D., PhD. Hospital Clinic, University of Barcelona
  More Information

Publications:
Responsible Party: Xavier Bosch, Dr., Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT01110824     History of Changes
Other Study ID Numbers: OVERCOME, 2007-006604-38, FIS EC07/90211
Study First Received: April 23, 2010
Last Updated: November 14, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Hospital Clinic of Barcelona:
Prevention
ventricular dysfunction
chemotherapy
acute myeloid leukemia
precursor-cell lymphoblastic leukemia
multiple myeloma
lymphoma
ejection fraction
Autologous hematopoietic stem cell transplantation

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Ventricular Dysfunction
Ventricular Dysfunction, Left
Blood Protein Disorders
Cardiovascular Diseases
Heart Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Carvedilol
Enalapril
Enalaprilat
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists

ClinicalTrials.gov processed this record on November 25, 2014