Udelson 2009.
| Methods | Randomized controlled trial | |
| Participants | The study location was the USA 136 participants on once‐daily medication were randomized to the intervention group and 133 participants on twice‐daily medication, and 136 on once‐daily medication + placebo participants were randomized to the control group The inclusion criteria were patients currently taking carvedilol IR twice‐daily with stable HF, who had mild, moderate, or severe symptoms and LV dysfunction. Patients were required to have been on stable dosing for at least 2 months without plans for further up‐titration. Stability of HF was defined as the absence of either a change in New York Heart Association class or a hospitalization for HF or administration of IV diuretics, vasodilators, or positive inotrope therapy during the 2 weeks before the screening/baseline visit; and a stable medical regimen receiving background HF medications as noted The exclusion criteria were patients with a history of symptomatic or sustained ventricular tachycardia or ventricular fibrillation within 3 months before screening |
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| Interventions | Intervention: ONCE‐DAILY DOSING
The intervention was an open‐label, once‐daily regimen of controlled‐release carvedilol CR Control: TWICE A DAY DOSAGE Participants received their usual twice‐daily dose of carvedilol IR, but in a double‐blinded fashion Control: ONCE A DAY DOSING PLUS PLACEBO Participants received a once‐daily dose of controlled release carvedilol CR in the morning with a placebo substituted for the second daily dose in a double‐blinded manner |
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| Outcomes | The measures of adherence were MEMS electronic measurement. Data were downloaded at months 1 and 5 The patient outcomes were evaluation and comparison of quality of life (QOL) measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), PHQ‐8 Depressive Symptoms Questionnaire (PHQ‐8), and Treatment Satisfaction Questionnaire with Medication. In addition, data were collected on BNP levels and hospital and emergency services utilization. After randomization, patients were seen at 1 month and again for the final visit at 5 months. Testing and administration of questionnaires were repeated at each of these visits |
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| Notes | ― | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomization was not described in detail. Eligible subjects were randomized in a 1:1:1 distribution to receive their usual twice‐daily dose of carvedilol IR, but in a double‐blinded fashion (Arm A) or (b) |
| Allocation concealment (selection bias) | Unclear risk | No information was provided about how allocation was handled. Eligible subjects were randomized in a 1:1:1 distribution to receive their usual twice‐daily dose of carvedilol IR, but in a double‐blinded fashion (Arm A) or (b) |
| Selective reporting (reporting bias) | Unclear risk | No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol |
| Other bias | Unclear risk | High level of baseline adherence use of MEMS; this obvious measure might have negated the blinding of control groups |
| Blinding of outcome assessment (detection bias) Adherence measure | Low risk | (PRIMARY) MEMS ‐ unlikely to be affected by lack of blinding of outcome assessors |
| Blinding of outcome assessment (detection bias) Patient outcome | Unclear risk | (PRIMARY) QUALITY OF LIFE (KCCQ) ‐ 2 of the 3 conditions were double‐blinded, but the other was not |
| Blinding of participants (performance bias) Adherence measure | High risk | (PRIMARY) MEMS ‐ MEMS is an obvious measure; patients are likely to be aware of measurement of adherence |
| Blinding of participants (performance bias) Patient outcome | High risk | (PRIMARY) QUALITY OF LIFE (KCCQ) ‐ This is a subjective measure; 2 of the 3 conditions were double‐blinded, but the other was not |
| Blinding of personnel (performance bias) Adherence measure | Low risk | (PRIMARY) MEMS ‐ Unlikely to be affected by lack of blinding of key study personnel |
| Blinding of personnel (performance bias) Patient outcome | Unclear risk | (PRIMARY) QUALITY OF LIFE (KCCQ) ‐ 2 of the 3 conditions were double‐blinded, but the other was not |
| Incomplete outcome data (attrition bias) Adherence measure | Low risk | (PRIMARY) MEMS ‐ Missing data are relatively balanced across the groups, with similar reasons (see table 2) |
| Incomplete outcome data (attrition bias) Patient outcome | Low risk | (PRIMARY) QUALITY OF LIFE (KCCQ) ‐ Dropouts are relatively balanced across groups with similar reasons |