Acute Myeloid LeukemiaPhase 3OVERCOMENCT01110824
Prevention of Left Ventricular Dysfunction During Chemotherapy
A Phase 3 study testing Enalapril and carvedilol in people with Acute Myeloid Leukemia and Precursor-cell Lymphoblastic Leukemia-Lymphoma, run by Hospital Clinic of Barcelona at 2 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia, Precursor-cell Lymphoblastic Leukemia-Lymphoma, Lymphoid Neoplasm
- What is being tested?
- Enalapril and carvedilol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesSpain
- Study dates
- Apr 2008to Mar 2012
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Congestive heart failure
- LVEF<50%
- Coronary artery disease,
- significant valvulopathy or myocardiopathy
- Renal failure (MDRD<30)
- Liver failure
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- 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
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Clinic
Barcelona, Catalonia, 08035
Hospital Clinic
Barcelona, Catalonia, 08036
About this study
Official title: Prevention of Left Ventricular Dysfunction With Enalapril and Carvedilol in Patients Submitted to Intensive Chemotherapy for the Treatment of Malignant Hemopathies
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia, Precursor-cell Lymphoblastic Leukemia-Lymphoma, Lymphoid Neoplasm, Multiple Myeloma, Lymphoma, Autologous Hematopoietic Stem Cell Transplantation
- Being tested
- Enalapril and carvedilol
- Keywords
- Prevention, ventricular dysfunction, chemotherapy, acute myeloid leukemia, precursor-cell lymphoblastic leukemia, multiple myeloma, lymphoma, ejection fraction, Autologous hematopoietic stem cell transplantation
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Multiple Myeloma, Lymphoma, Ventricular Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enalapril and carvedilolDrug
Enalapril 2.5 to 10 mg BID Carvedilol 6.25 to 25 mg BID
| Study group | Role | What they receive |
|---|---|---|
| Enalapril and carvedilol | Experimental | Enalapril 2.5 to 10 mg BID plus Carvedilol 6.25 to 25 mg BID Receives: Drug: Enalapril and carvedilol |
| Control | No intervention | Control arm without intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in left ventricular ejection fraction (LVEF) measured by echocardiography and by cardiac magnetic resonance imaging (CMR).
Measured: 6 months after randomization
Secondary outcomes (8)
Incidence of death, heart failure or LV systolic disfunction (LVEF<45%)
Measured: 6 months after randomization
Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity
Measured: Baseline
Prognostic value for cardiac toxicity of troponin I and BNP
Measured: up to 3 months
Right and left ventricular volumes measured by CMR
Measured: 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).
Measured: 6 months after randomization
Incidence of an absolute decrease in LVEF>10 percent units associated with a decline below its normal limit of 50%
Measured: 6 months after randomization
Serious adverse events
Measured: 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
Measured: 6 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2010 (estimated)
- Study startApr 2008
- Primary completionDec 2011
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III, European Union
- Responsible party
- Principal investigator, Xavier Bosch, Hospital Clinic of Barcelona
- Investigators
- Xavier Bosch, M.D., PhD., Study chair, Hospital Clinic, University of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110824
- Sponsor's protocol ID
- OVERCOME
- Other IDs
- 2007-006604-38, FIS EC07/90211
- Acronym
- OVERCOME
- Status last verified
- Nov 2013
- First submitted
- 23 Apr 2010
- Last updated
- 15 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21807325Bosch 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.
PubMed 23583763