NCT01110824

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Apr 2008

Typical duration for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2008

Completed
2.1 years until next milestone

First Submitted

Initial submission to the registry

April 23, 2010

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 27, 2010

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2011

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed
Last Updated

November 15, 2013

Status Verified

November 1, 2013

Enrollment Period

3.7 years

First QC Date

April 23, 2010

Last Update Submit

November 14, 2013

Conditions

Keywords

Preventionventricular dysfunctionchemotherapyacute myeloid leukemiaprecursor-cell lymphoblastic leukemiamultiple myelomalymphomaejection fractionAutologous hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

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

    6 months after randomization

Secondary Outcomes (8)

  • Incidence of death, heart failure or LV systolic disfunction (LVEF<45%)

    6 months after randomization

  • Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity

    Baseline

  • Prognostic value for cardiac toxicity of troponin I and BNP

    up to 3 months

  • Right and left ventricular volumes measured by CMR

    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).

    6 months after randomization

  • +3 more secondary outcomes

Study Arms (2)

Enalapril and carvedilol

EXPERIMENTAL

Enalapril 2.5 to 10 mg BID plus Carvedilol 6.25 to 25 mg BID

Drug: Enalapril and carvedilol

Control

NO INTERVENTION

Control arm without intervention

Interventions

Enalapril 2.5 to 10 mg BID Carvedilol 6.25 to 25 mg BID

Enalapril and carvedilol

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Hospital Clinic

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic

Barcelona, Catalonia, 08036, Spain

Location

Related Publications (2)

  • Bosch X, Esteve J, Sitges M, de Caralt TM, Domenech A, Ortiz JT, Monzo M, Morales-Ruiz M, Perea RJ, Rovira M. Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial. J Card Fail. 2011 Aug;17(8):643-8. doi: 10.1016/j.cardfail.2011.03.008. Epub 2011 May 6.

    PMID: 21807325BACKGROUND
  • Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, Morales-Ruiz M, Perea RJ, Monzo M, Esteve J. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013 Jun 11;61(23):2355-62. doi: 10.1016/j.jacc.2013.02.072. Epub 2013 Apr 10.

MeSH Terms

Conditions

Leukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaMultiple MyelomaLymphomaVentricular Dysfunction

Interventions

EnalaprilCarvedilol

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersHeart Diseases

Intervention Hierarchy (Ancestors)

DipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and ProteinsPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesCarbazolesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHeterocyclic Compounds, 3-Ring

Study Officials

  • Xavier Bosch, M.D., PhD.

    Hospital Clinic, University of Barcelona

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr.

Study Record Dates

First Submitted

April 23, 2010

First Posted

April 27, 2010

Study Start

April 1, 2008

Primary Completion

December 1, 2011

Study Completion

March 1, 2012

Last Updated

November 15, 2013

Record last verified: 2013-11

Locations