Pruthi 2007.

Methods	Open‐label multicentre RCT.
Participants	24 male participants with congenital haemophilia A or B with inhibitors undergoing elective major surgery receiving recombinant FVIIa (rFVIIa) as bolus or continuous infusion for the efficacy outcomes. 12 males with congenital haemophilia A or B without inhibitors undergoing elective major surgery as control group for safety assessment. Age: median (range) 37.4 (10 ‐ 67) years and 26.7 (11 ‐ 53) years in the 2 treatment inhibitor groups; 31 (14 ‐ 76) years in the control non‐inhibitor group.
Interventions	Bolus infusion: 90 μg/kg rFVIIa every 2 hours during surgery through day 5, then every 4 hours for days 6 ‐ 10. Continuous infusion: 50 μg/kg/hour through day 5, then 25 μg/kg/hour for days 6 ‐ 10. All inhibitor participants received an initial bolus dose of 90 μg/kg rFVIIa. Two additional rFVIIa bolus infusions for breakthrough bleeding allowed in any 24‐hour period. The control group (safety assessment) received FVIII or FIX concentrates per institutional protocols.
Outcomes	Primary efficacy outcome Subjective investigator's assessment of treatment efficacy (2‐level: effective or ineffective) at the time of discontinuation of therapy or at post‐operative day 10. Haemostasis assessment at wound closure (0 hours), at 8, 24, 48, 72 hours following wound closure and daily until discharge or post‐operative day 10. Safety: clinical symptoms; concomitant medications; and adverse events.
Notes	Sample size not sufficient for adequate statistical power in either efficacy and safety analysis . One participant in the bolus infusion arm excluded from efficacy analysis because of acquired haemophilia. 2 surgeries (1 in each arm) considered as minor. Dosages of rFVIIa, length of treatment and FVII activity levels were also evaluated. Greater mean total dose of rFVIIa was administered during the intra‐operative period and up to 72 post‐operative hours in the continuous infusion arm.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Central randomisation. No further details provided.
Allocation concealment (selection bias)	Unclear risk	Central randomisation, open‐label treatment. No further details reported.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding was not possible for physicians and participants because of the different modality of administration.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcome was assessed by the investigators, who were not blinded of administered treatment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT population for the efficacy analysis (one participant in the bolus infusion arm excluded). 6 participants (3 bolus infusion, 3 continuous infusion), who discontinued from the trial because of ineffective haemostasis, were reported in the efficacy analysis.
Selective reporting (reporting bias)	Low risk	Outcome data reported in the methods and results sections correspond.
Other bias	High risk	Subjective assessment for the primary efficacy endpoint. Number of additional rFVIIa higher in the bolus infusion than in the continuous infusion arm [mean (range) 2.6 (0 ‐ 5) vs 1.4 (0 ‐ 3)]. Trend to younger age of participants in the continuous infusion arm (mean 26.7, range 11 ‐ 53; vs 37.4, 10‐67 in the bolus infusion arm). No data on inhibitor titres provided.