VMAC 2002.
| Study characteristics | ||
| Methods | Prospective, multi‐centre trial | |
| Participants | Patients were randomised, of which 489 were treated with study drug (143 nitroglycerin, 204 nesiritide and 142 placebo) at 55 centres. All patients had dyspnoea at rest (or New York Heart Association class IV symptoms) at study entry, 84% had chronic decompensated CHF that was classified as class III or class IV prior to decompensation, and most had clinical evidence of fluid overload) | |
| Interventions | Intravenous nesiritide (n = 204), intravenous nitroglycerin (n = 143) or placebo (n = 142) added to standard medications for 3 hours, followed by nesiritide (n = 278) or nitroglycerin (n = 216) added to standard medication for 24 hours | |
| Outcomes | Primary outcome measure: change in pulmonary capillary wedge pressure (PCWP) among catheterised patients and patient self evaluation of dyspnoea at 3 hours after initiation of study drug among all patients Secondary outcomes included comparisons of haemodynamic and clinical effects between nesiritide and nitroglycerin at 24 hours |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Randomization occurred after patients were confirmed to meet all inclusion and exclusion criteria and informed consent was obtained. ... Non catheterized patients were randomly assigned to receive either placebo, nitroglycerin… Catheterized patients were randomly assigned to these same 3 treatment groups or to the adjustable‐dose nesiritide group. For placebo patients in both strata, the randomization included a crossover to double blind treatment with either titratable dose or to fixed‐dose nesiritide at 3 hours…” |
| Allocation concealment (selection bias) | Low risk | Quote: "Randomization was performed using random permuted blocks within strata (catherized or non‐catherized), with a block size of 8 for the catheterized strata and of 6 for the noncathereterized strata. Non catheterized patients were randomly assigned to receive either placebo, nitroglycerin… Catheterized patients were randomly assigned to these same 3 treatment groups or to the adjustable‐dose nesiritide group. For placebo patients in both strata, the randomization included a crossover to double blind treatment with either titratable dose or to fixed‐dose nesiritide at 3 hours…” |
| Blinding (performance bias and detection bias) | Low risk | Quote: "The study used a double‐blind, double‐dummy study drug administration design in which each patient received simultaneous infusions of nitroglycerin/placebo and nesiritide/placebo.” |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: small numbers 2 to 4 (per group) did not receive the study drug as assigned |
| Selective reporting (reporting bias) | Low risk | The study protocol is available and all of the study's pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way |
| Other bias | Low risk | The study appears to be free of other major sources of bias |
BP: blood pressure CHF: congestive heart failure ED: emergency department IV: intravenous NAC: N‐acetylcysteine NTG: nitroglycerin