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Prevention of Left Ventricular Dysfunction During Chemotherapy (OVERCOME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01110824
Recruitment Status : Completed
First Posted : April 27, 2010
Last Update Posted : November 15, 2013
Instituto de Salud Carlos III
European Union
Information provided by (Responsible Party):
Xavier Bosch, Hospital Clinic of Barcelona

Brief Summary:

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : April 2008
Actual Primary Completion Date : December 2011
Actual Study Completion Date : March 2012

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Incidence of death, heart failure or LV systolic disfunction (LVEF<45%) [ Time Frame: 6 months after randomization ]
  2. Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity [ Time Frame: Baseline ]
  3. Prognostic value for cardiac toxicity of troponin I and BNP [ Time Frame: up to 3 months ]
  4. Right and left ventricular volumes measured by CMR [ Time Frame: 6 months after randomization ]
  5. 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 ]
  6. 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 ]
  7. Serious adverse events [ Time Frame: 6 months after randomization ]
  8. 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 ]

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01110824

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

Publications of Results:
Other Publications:
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Responsible Party: Xavier Bosch, Dr., Hospital Clinic of Barcelona Identifier: NCT01110824     History of Changes
Other Study ID Numbers: OVERCOME
2007-006604-38 ( EudraCT Number )
FIS EC07/90211 ( Other Grant/Funding Number: ISCIII )
First Posted: April 27, 2010    Key Record Dates
Last Update Posted: November 15, 2013
Last Verified: November 2013
Keywords provided by Xavier Bosch, Hospital Clinic of Barcelona:
ventricular dysfunction
acute myeloid leukemia
precursor-cell lymphoblastic leukemia
multiple myeloma
ejection fraction
Autologous hematopoietic stem cell transplantation
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Multiple Myeloma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Ventricular Dysfunction
Ventricular Dysfunction, Left
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Heart Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents