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. 2016 Jul 8;2016(7):CD009077. doi: 10.1002/14651858.CD009077.pub3

Botoni 2007.

Methods

  1. Design: parallel (2 arms)

  2. Country: Brazil

  3. Multicenter: no

  4. International: no

  5. Follow‐up period: 4 months
Participants

  • Enrolled: 42

  • Lost participants before randomisation: 7.1% (3/42)

  •  Randomized: 39

  1. Carvedilol group: 19

  2. Placebo group:  20

  •  Receiving drug: 39

  1. Carvedilol group: 19 (48.7%)

  2. Placebo group: 20 (51.3%)

  • Lost post randomisation: 24% (3/39)

  1. Carvedilol group: 5.2% (1/19)

  2. Placebo group: 10% (2/20)

  3. Imbalance between comparison groups: 4.8%

  • Analysed:

  1. Carvedilol group: 18 (95%)

  2. Placebo group: 18 (90%)

  • Age (years SD):

  1. Overall group: Baseline: 47.8 (10.4)

  2. Overall group: After RAS inhibition: 48.2 (10.4)

  •  Gender (male):

  1. Overall group: baseline: 71.4% (30/42)

  2. Overall group: after RAS inhibition: 69.2% (27/39)

  •  Inclusion criteria:

  1. Positive for T. cruzi as confirmed by 2 or more serological tests (indirect immunofluorescence, ELISA, indirect hemagglutination);

  2. Cardiomyopathy when at least 3 of the following criteria were fulfilled: Left ventricular end diastolic diameter (LVDD) N55 mm; LVDD/body surface area N2.7cm/m²; left ventricular ejection fraction (LVEF) b55%; QRS interval N120 ms; echocardiographic evidence of diffuse or segmental systolic wall motion abnormalities.

  • Exclusion criteria:

  1. Pregnant;

  2. Using any beta‐blocker;

  3. Hypertension, diabetes mellitus, thyroid dysfunction, chronic obstructive pulmonary disease, asthma, renal or hepatic failure.
Interventions

  1. Experimental: carvedilol 3.125 mg and up‐titrated every 15 days to 25 mg twice a day. Duration: 4 months

  2. Control: placebo. Details not stated. Nature of placebo: not stated.

  3. Co‐intervention: enalapril was started at 5 mg and up‐titrated weekly to 20 mg twice a day. Spironolactone was given at a dose of 25 mg once a day. In cases of intolerance, characterized by cough or angioedema, enalapril was replaced with losartan 50 mg once a day. (page 544.e2)
Outcomes

  • Primary:

  1. Change in left ventricular ejection fraction.

  • Secondary:

  1. Changes in other echocardiographic parameters;

  2. Framingham score;

  3. Quality of life (36‐item Short‐Form Health Survey);

  4. New York Heart Association class;

  5. Radiographic indices;

  6. Brain natriuretic peptide levels, chemokines;

  7. Safety.
Notes

  1. ClinicalTrials.gov Identifier: NCT01557140

  2. Sample size estimation a priori: yes

  3. Date of Trial: May 2003 and March 2004.

  4. Sponsor: Baldacci Pharmaceutical Laboratory and FUNED (Fundacao Ezequiel Dias)

  5. Rol of sponsor: carvedilol and placebo were supplied by Baldacci Pharmaceutical Laboratory and FUNED (Fundacao Ezequiel Dias), respectively

  6. Conflict of interest: none stated.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote: "Randomization was achieved by each patient selecting an envelope that contained a number. The number was sent to the pharmacist, who provided the appropriate medication box to each patient. The medication container was identified only by each patient's name." (page 544e2)
Allocation concealment (selection bias) Unclear risk Quote: "Randomization was achieved by each patient selecting an envelope that contained a number. The number was sent to the pharmacist, who provided the appropriate medication box to each patient. The medication container was identified only by each patient's name." (page 544e2)
Blinding of participants and personnel (performance bias) 
 All outcomes Unclear risk Quote: “…the patients were assigned in a double blind fashion to receive either placebo or carvedilol... each patient selecting an envelope that contained a number. The number was sent to the pharmacist, who provided the appropriate medication box to each patient. The medication container was identified only by each patient's name." (page 544e2)
Blinding of outcome assessment (detection bias) 
 All outcomes Unclear risk Insufficient information to permit judgment of 'low risk' or 'high risk'
Incomplete outcome data (attrition bias) 
 All outcomes High risk Loss of participants before randomisation: 7.1% (3/42)
Lost post‐randomisation: 24% (3/39)
 Carvedilol group: 5.2% (1/19)
 Placebo group: 10% (2/20)
 Imbalance between comparison groups: 4.8%
 
Quote: “Three patients were lost in phase 1, each because of sudden death, poorly controlled ventricular tachycardia, and noncompliance. Of the 39 patients who entered phase II, 20 were randomised to receive placebo and 19 were randomised to receive carvedilol. Two patients from the placebo group were lost, each because of death caused by intractable HF and intolerable symptoms. One patient from the carvedilol group died suddenly." (page 544e5‐544e6)
Selective reporting (reporting bias) High risk The study report failed to include results for a key outcome that would be expected to have been reported for such a study.
Other bias High risk Industry bias