Antunes 2014.
| Methods | Multicenter parallel randomized study conducted in 17 centres in Bulgaria, Russia, Croatia, Poland, Romania, USA, Japan and Brazil | |
| Participants | 36 males (prophylaxis (n = 17) or on‐demand therapy (n = 19)) Inclusion criteria: hemophilia A or B with documented history of high‐titre inhibitor (> 5 BU/mL) or low‐titre inhibitor (≤ 5 BU/mL) refractory to increased dosing of either FVIII or FIX for at least 12 months; were ≥ 4 and ≤ 65 years of age; were currently being treated on demand with bypassing agents; had ≥ 12 bleeding episodes in the previous 12 months; and a negative HIV status, or if positive, with a stable CD4 count Exclusion criteria: symptomatic liver disease; had platelet count < 100,000 per μL; were currently receiving ITI or prophylaxis; needed elective surgery; needed alpha‐interferon or protease inhibitor use; or had previous thromboembolic events |
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| Interventions | Prophylaxis: FEIBA NF 85 +/‐ 15 units/kg intravenously bolus infusion every other day On demand: FEIBA NF, dosing depended on type of bleeding and was at discretion of the investigator Duration of treatment: 12 months (+/‐ 14 days) |
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| Outcomes | Primary outcome: annualised bleeding rate Secondary outcomes: AJBR, overall bleeding events, target joint bleeding events, occurrence of new target joints, hemostatic efficacy, total FEIBA NF utilization, safety and quality of life |
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| Notes | Study sponsored by Baxter Healthcare Corporation | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Block randomization in a 1:1 ratio with stratification by geography (block size not stated) |
| Allocation concealment (selection bias) | Low risk | The randomization scheme was centralized |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Open‐label study |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Open‐label study |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 2 participants withdrew from on‐demand group (1 serious adverse event and 1 surgery) and 1 from the prophylaxis group (adverse event). Withdrawal rate similar across groups and all participants included in an ITT analysis |
| Selective reporting (reporting bias) | Low risk | No protocol available. All outcomes defined in the methods reported in the results, no evidence of selective reporting |
| Other bias | Low risk | None identified |