Chagas CardiomyopathyPhase 4NCT01557140
A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
A Phase 4 study testing RASi plus carvedilol in people with Chagas Cardiomyopathy and Heart Failure, run by Federal University of Minas Gerais at 1 site in Brazil.
Trial summary
Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chagas Cardiomyopathy, Heart Failure, Dilated Cardiomyopathy
- What is being tested?
- RASi plus carvedilol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteBrazil
- Study dates
- May 2003to Dec 2006
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Criteria for inclusion were positivity for T cruzi as confirmed by 2 or more serological tests (indirect immunofluorescence, ELISA, and/or indirect hemagglutination) and having cardiomyopathy.
- Cardiomyopathy was present when at least 3 of the following criteria were fulfilled:
- LV enddiastolic diameter (LVDD) N55 mm
- LVDD/body surface area > 2.7cm/m2
- LV ejection fraction (LVEF) < 55%
- QRS interval > 120 ms
- echocardiographic evidence of diffuse or segmental systolic wall motion abnormalities.
Who cannot join
- Using any h-blocker
- Having additional comorbidities (eg, hypertension, diabetes mellitus, thyroid dysfunction, chronic obstructive pulmonary disease, asthma, and renal or hepatic failure).
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Chagas Disease Outpatient Center of the Federal University of Minas Gerais
Belo Horizonte, Minas Gerais
About this study
Official title: A Randomized Trial of Carvedilol After Renin-angiotensin System Inhibition in Chronic Chagas Cardiomyopathy
Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. Hence, the objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy. This way, the investigators conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.
Read the detailed description
Chronic Chagas cardiomyopathy (CCC) is an important cause of heart failure (HF) and sudden death in Latin America.1 According to recent estimates, 13 million people worldwide are infected with Trypanosoma cruzi, of whom 3.0 to 3.3 million are symptomatic.2 The incidence rate is 200000 cases per year. Among those infected, 30% have clinical features of CCC and 15% ultimately develop overt left ventricular (LV) insufficiency-the main prognostic determinant of the disease. In Chagas cardiomyopathy, the hemodynamic and neurohormonal responses do not differ from those in other cardiomyopathies. This common pathophysiology suggests that treatments shown to be effective by classic HF trials should be beneficial in CCC. However, CCC has several specific characteristics, such as early cardiac denervation, frequent ventricular arrhythmias, and several forms as well as grades of conduction disturbances, including sinus bradycardia, complete atrioventricular block, and right bundle-branch block. Morphologically, hypertrophy, dilatation, and severe fibrosis are prominent. In 20% to 40% of cases, an apical ventricular aneurysm is present.1 These peculiarities in combination lead to a high incidence of sudden death (60% of all deaths), cardiac insufficiency, and ventricular remodeling. The responses of patients to the usual drugs prescribed in HF could be different, and this perception has led to the suboptimal dosing or lack of initiation of medical treatments that are of proven efficacy in patients with other etiologies of HF. The underlying problem is that therapies that are effective in patients with HF caused by non-chagasic cardiomyopathies, such as those with renin-angiotensin system inhibitors (RASis) and h-blockers, have yet to be formally tested in CCC. There are few clinical trials and no randomized study on this subject. Consequently, the investigators evaluated the effects of optimizing treatment with enalapril and spironolactone and then undertook a randomized trial of adding a h-blocker in the treatment of patients with CCC.
- Conditions
- Chagas Cardiomyopathy, Heart Failure, Dilated Cardiomyopathy
- Being tested
- RASi plus carvedilol
- Keywords
- Chagas cardiomyopathy,, Renin-angiotensin system,, Beta-blockers,, Enalapril,, Carvedilol,, Renin-angiotensin system inhibitors,, Brain natriuretic peptide level,, Left ventricular ejection fraction,, Chemokines
- Medical subject headings
- Chagas Cardiomyopathy, Heart Failure, Cardiomyopathy, Dilated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RASi plus carvedilolDrug
Also called Randomized, Double blind, Controlled, Trial
Patients were randomly assigned to 2 groups, with 1 group receiving renin-angiotensin system inhibitors (enalapril) plus carvedilol and the other receiving renin-angiotensin system inhibitors (enalapril) plus placebo
| Study group | Role | What they receive |
|---|---|---|
| RASi plus placebo | Placebo comparator | RAS inhibition was optimized and after patients were randomly assigned to receive placebo |
| RASi plus carvedilol | Experimental | RAS inhibition was optimized and after patients were randomly assigned to receive carvedilol Receives: Drug: RASi plus carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in left ventricular ejection fraction
Measured: Baseline, 4 months and 8 months
Secondary outcomes (8)
Changes in Framingham score
Measured: Baseline, 4 months and 8 months
Changes in quality of life (36-item Short-Form Health Survey)
Measured: Baseline, 4 months and 8 months
Changes in New York Heart Association functional class
Measured: Baseline, 4 months and 8 months
Changes in cardiothoracic ratio
Measured: Baseline, 4 months and 8 months
Changes in echocardiographic diastolic function indices
Measured: Baseline, 4 months and 8 months
Changes in brain natriuretic peptide levels
Measured: Baseline, 4 months and 8 months
Changes in chemokines
Measured: Baseline, 4 months and 8 months
Changes in autoantibodies levels
Measured: Baseline, 4 months and 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2012 (estimated)
- Study startMay 2003
- Primary completionMar 2004
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chagas CardiomyopathyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of Minas Gerais
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais
- Investigators
- Fernando A Botoni, MD, PhD, Principal investigator, Federal University of Minas Gerais
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01557140
- Sponsor's protocol ID
- Carvedilol in Chagas disease
- Status last verified
- Aug 2015
- First submitted
- 21 Feb 2012
- Last updated
- 13 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto AS, Teixeira MM, Teixeira AL Jr, Reis AM, Dantas JB, Ferreira CS, Tavares WC Jr, Rocha MO. A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. Am Heart J. 2007 Apr;153(4):544.e1-8. doi: 10.1016/j.ahj.2006.12.017.
PubMed 17383291
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Carvedilol After Renin-angiotensin System Inhibition in Chronic Chagas Cardiomyopathy
- ClinicalTrials.gov ID
- NCT01557140
- Acronym / sponsor ID
- Carvedilol in Chagas disease
- Conditions
- Chagas Cardiomyopathy, Heart Failure, Dilated Cardiomyopathy
- Keywords
- Chagas cardiomyopathy,, Renin-angiotensin system,, Beta-blockers,, Enalapril,, Carvedilol,, Renin-angiotensin system inhibitors,, Brain natriuretic peptide level,, Left ventricular ejection fraction,
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Federal University of Minas GeraisUniversity, hospital or other
- Study start
- May 2003
- Primary completion
- Mar 2004 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 19 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. Hence, the objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy. This way, the investigators conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.
Detailed description
Chronic Chagas cardiomyopathy (CCC) is an important cause of heart failure (HF) and sudden death in Latin America.1 According to recent estimates, 13 million people worldwide are infected with Trypanosoma cruzi, of whom 3.0 to 3.3 million are symptomatic.2 The incidence rate is 200000 cases per year. Among those infected, 30% have clinical features of CCC and 15% ultimately develop overt left ventricular (LV) insufficiency-the main prognostic determinant of the disease. In Chagas cardiomyopathy, the hemodynamic and neurohormonal responses do not differ from those in other cardiomyopathies. This common pathophysiology suggests that treatments shown to be effective by classic HF trials should be beneficial in CCC. However, CCC has several specific characteristics, such as early cardiac denervation, frequent ventricular arrhythmias, and several forms as well as grades of conduction disturbances, including sinus bradycardia, complete atrioventricular block, and right bundle-branch block. Morphologically, hypertrophy, dilatation, and severe fibrosis are prominent. In 20% to 40% of cases, an apical ventricular aneurysm is present.1 These peculiarities in combination lead to a high incidence of sudden death (60% of all deaths), cardiac insufficiency, and ventricular remodeling. The responses of patients to the usual drugs prescribed in HF could be different, and this perception has led to the suboptimal dosing or lack of initiation of medical treatments that are of proven efficacy in patients with other etiologies of HF. The underlying problem is that therapies that are effective in patients with HF caused by non-chagasic cardiomyopathies, such as those with renin-angiotensin system inhibitors (RASis) and h-blockers, have yet to be formally tested in CCC. There are few clinical trials and no randomized study on this subject. Consequently, the investigators evaluated the effects of optimizing treatment with enalapril and spironolactone and then undertook a randomized trial of adding a h-blocker in the treatment of patients with CCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RASi plus placebo | Placebo comparator | –RAS inhibition was optimized and after patients were randomly assigned to receive placebo |
| RASi plus carvedilol | Experimental | Drug: RASi plus carvedilolRAS inhibition was optimized and after patients were randomly assigned to receive carvedilol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Criteria for inclusion were positivity for T cruzi as confirmed by 2 or more serological tests (indirect immunofluorescence, ELISA, and/or indirect hemagglutination) and having cardiomyopathy.
- Cardiomyopathy was present when at least 3 of the following criteria were fulfilled:
Key exclusion criteria (2 listed)
- Using any h-blocker
- Having additional comorbidities (eg, hypertension, diabetes mellitus, thyroid dysfunction, chronic obstructive pulmonary disease, asthma, and renal or hepatic failure).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RASi plus carvedilolAlso: Randomized, Double blind, Controlled, TrialPatients were randomly assigned to 2 groups, with 1 group receiving renin-angiotensin system inhibitors (enalapril) plus carvedilol and the other receiving renin-angiotensin system inhibitors (enalapril) plus placebo | Drug | RASi plus carvedilol |
Primary outcome
Changes in left ventricular ejection fraction
Time frame: Baseline, 4 months and 8 months
8 secondary outcomes
Changes in Framingham score
Time frame: Baseline, 4 months and 8 months
Changes in quality of life (36-item Short-Form Health Survey)
Time frame: Baseline, 4 months and 8 months
Changes in New York Heart Association functional class
Time frame: Baseline, 4 months and 8 months
Changes in cardiothoracic ratio
Time frame: Baseline, 4 months and 8 months
Changes in echocardiographic diastolic function indices
Time frame: Baseline, 4 months and 8 months
Changes in brain natriuretic peptide levels
Time frame: Baseline, 4 months and 8 months
Changes in chemokines
Time frame: Baseline, 4 months and 8 months
Changes in autoantibodies levels
Time frame: Baseline, 4 months and 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
- Results publication: PubMed 17383291Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto AS, Teixeira MM, Teixeira AL Jr, Reis AM, Dantas JB, Ferreira CS, Tavares WC Jr, Rocha MO. A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. Am Heart J. 2007 Apr;153(4):544.e1-8. doi: 10.1016/j.ahj.2006.12.017.
Related trials for Chagas Cardiomyopathy
Recruiting
Cardiac Contractility Modulation in Chagas Heart Disease
Chagas Cardiomyopathy, Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fernando A Botoni, MD, PhD principal investigator
Federal University of Minas Gerais
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing RASi plus carvedilol in people with Chagas Cardiomyopathy and Heart Failure, run by Federal University of Minas Gerais at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in left ventricular ejection fraction (time frame: Baseline, 4 months and 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01557140, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2015.