Chagas Cardiomyopathy Bisoprolol Intervention Study: Charity

NCT00323973 | Completed Phase 3 DMC

• 1 other identifier: fcv059
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Chagas disease (CD) is the major cause of disability secondary to tropical diseases in young adults from Latin America. In this region 20 million people are currently infected by T. cruzi, the etiologic agent for CD. In Colombia, 18 percent of the population live in CD endemic areas, 900,000 people are infected and over three million are at high risk of being infected. Heart failure due to Chagas cardiomyopathy (CCM) is the main clinical form of CD in Colombia. However, the incidence of CCM among T. cruzi infected people is unknown and the mechanisms that lead from infection to CCM are uncertain. Besides the poor prognosis of CHF due to Chagas disease, it is important to estimate the risk of complications and death in patient infected with T. cruzi Unfortunately, few clinical studies have addressed this issue. Most T. cruzi infected patients have mild or no clinical disease, however, the percentage of infected people that will develop detectable cardiac abnormalities is approximately 30 to 40 percent, but only 20 percent of them will develop symptomatic cardiac involvement. Like CHF from other causes, CHF due to CD responds to digital, diuretics and vasodilators therapy. Also, some studies have shown that angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with moderate to severe CHF due to CD. Increased sympathetic drive results in an increased risk of cardiac arrhythmia and sudden death. Beta-adrenoreceptor antagonism seems to protect against the deleterious effects of chronic sympathetic stimulation. The effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with CHF secondary to CCM has not been explored to-date. To evaluate the benefit of Bisoprolol in CHF due to CCM, a cohort of T. cruzi seropositive patients will be selected from several institutions in Colombia. Patients will be classified according to a modified version of the Panamerican Health Organization recommendations for patients with CCM. Overall one year mortality in patients with CHF due to Chagas disease has been reported as 34 percent. However, one year mortality is only 3 percent in patients in NYHA functional class II, 27 percent in those in NYHA functional class III, and 62 percent among those in functional class IV (22). The sample size has been calculated assuming an event rate of 40 percent in two years in the placebo group, and using a 95 percent confidence level and power of 80 percent, we will need to recruit 250 patients per treatment arm to detect a reduction of 30 percent in the risk of the primary outcome. The event rate we have used to estimate sample size is similar to the expected two-year mortality in patients with CHF due to Chagas disease in NYHA functional class II. Therefore, the estimated sample size should be enough to measure significant changes in the composite primary outcome (death, HF hospitalizations, SMVT, SCD). The recruitment process will follow guidelines set out by the FCV Ethics Committee. Most participants will be recruited from the Chagas disease and the Heart Failure clinics located in Bucaramanga, Bogotá and Cucuta. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms, baseline measurements and tests will be conducted at the FCV including blood pressure measurements obtained with patients in the sitting and standing positions. Laboratory test such as twelve-lead ECG will be recorded in each patient. Left ventricular ejection fraction at rest will be determined by 2D echocardiography, using a modified Simpsons rule to calculate LV volumes. Quality of life questionnaire will be performed two weeks apart during baseline examination using the Minnesota living with heart failure questionnaire. Minimum of two 6-minutes corridor walk test once a week over a two-week period will be performed to measure the functional class. During the treatment period patients will be randomly assigned to receive double-blind Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5 up to 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. Following the descriptive analysis we will compare the patient survival and hospitalization rates using Kaplan-Meier estimates and survival graphs. Cox regression will be used for the multivariate analysis of time to death and time to hospitalization. This analysis will allow us to explore the pattern of changes in patients with chronic heart failure due to Chagas disease such as the effect of beta-blockers in this special type of cardiomyopathy.

Conditions

Chagas Cardiomyopathy; Chronic Heart Failure

Keywords

Chagas, Heart failure, Cardiomiopathy

Outcome Measures

Primary Outcomes (4)

• Hospital admission caused by heart failure.

  2 years

• Major adverse cardiovascular events: stroke, systemic embolism, resuscitated sudden death.

  2 years

• Bradycardia requiring pacemaker implantation.

  2 years

• Clinically significant sustained monomorphic ventricular tachycardia causing syncope: sustained ventricular tachycardia or ventricular fibrillation.

  2 years

Secondary Outcomes (5)

• Non-cardiovascular death.

  2 years

• Heart failure worsening or mortality related with CHF.

  2 years

• New AV block.

  2 years

• Need for Implantable cardioverter-defibrillator (ICD), Cardiac resynchronization Therapy (CRT) or Pacemaker therapy (PM).

  2 years

• Perceived quality of life worsening.

  2 years

Study Arms (2)

1

EXPERIMENTAL

Drug: Bisoprolol

2

PLACEBO COMPARATOR

Placebo

Drug: Bisoprolol

Interventions

Bisoprolol DRUG

10 mg qd

Also known as: Bisoprex

1; 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 18 to 70 years.
• Heart failure symptoms NYHA functional class II to IV
• Left ventricular ejection fraction \<40% determined by bi-dimensional echocardiography using modified Simpson's rule for ventricular volumes.
• Subjects must be on standard and stable outpatient doses of ACEIs or angiotensin II receptor antagonist for at least four weeks.
• Subjects receiving diuretics must be on a stable dose for at least two weeks.
• Clinical Euvolemia:as evidenced by absence of rales, no pleural effusion or ascitis and no more than minimal peripheric edema.

You may not qualify if:

• CHF due to ischemic heart disease, valvular disease or any other etiology different than CD.
• Severe aortic insufficiency
• Baseline advanced AV block defined as Mobitz type 2 or third degree AV block
• Serum creatinine \>2.5 mg/dl.
• Resting Heart rate less \< 45 bpm
• Known malignancy and other severe disease which shorten life expectancy \< 6 months.
• Subjects with contraindications for beta-blockers: severe obstructive chronic pulmonary disease, asthma, severe pulmonary hypertension, type 1 diabetes mellitus or history of hypoglicemia.
• Suspected or confirmed chronic infectious disease including HIV and hepatitis B.
• History of active substance or alcohol abuse within the last year.
• Clinically significant psychiatric illness which can negatively affect the subject compliance and participation in the trial.
• Pregnancy or lactation.
• Organic disease or gastrointestinal surgery which can affect the oral absorption and pharmacodynamics of the medication under study.
• Enrollment and participation in other active treatment trial within the previous month.
• Failure to provide written informed consent.

Sponsors & Collaborators

• Fundación Cardiovascular de Colombia: lead

Study Sites (1)

Fundación Cardiovascular de Colombia

Floridablanca, Santander Department, 10000, Colombia

Location

MeSH Terms

Conditions

Chagas Cardiomyopathy; Heart Failure

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Chagas Disease; Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Carlos A Morillo, MD, FRCPC

  Fundación Cardiovascular de Colombia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 5, 2006
• First Posted: May 10, 2006
• Study Start: July 1, 2003
• Primary Completion: July 1, 2005
• Study Completion: July 1, 2006
• Last Updated: November 24, 2010

Record last verified: 2010-11

Locations

CO (1)