Skolnick 2014.
| Methods | Multicentre randomised, double‐blind, placebo‐controlled phase III study | |
| Participants | Acute severe TBI patents, aged 16‐70 years (GCS score, ≤ 8 and at least 1 reactive pupil) | |
| Interventions | Both groups: The study drugs (progesterone and placebo) were provided in 250 ml bottles with identical appearance, containing a lipid emulsion consisting of 6% soybean oil and 1.2% egg lecithin phospholipids with the addition of 2.0 mg of progesterone per ml for the active treatment (BHR‐100, Fresenius Kabi). Drug infusion (progesterone or placebo) was started intravenously with 0.355 ml/kg/h for 1 h, followed by 0.25 ml/kg/h for 119 hours, through a dedicated peripheral intravenous catheter or dedicated lumen of a multilumen central catheter. | |
| Outcomes | Primary: GOS at 6 months Secondary: mortality and adverse events |
|
| Notes | Funded by BHR Pharma; Clinicaltrials.gov number, NCT01143064 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Randomization was implemented with the use of an interactive Web‐based response system, with a block design of four stratified according to geographic region (Asia, Europe, North America, and South America)." (p 2469) Comment: probably done |
| Allocation concealment (selection bias) | Low risk | Quote: "Randomization was implemented with the use of an interactive Web‐based response system, with a block design of four stratified according to geographic region (Asia, Europe, North America, and South America)." (p 2469) Quote: "The study drugs (progesterone and placebo) were provided in 250‐ml bottles with identical appearance, containing a lipid emulsion consisting of 6% soybean oil and 1.2% egg lecithin phospholipids, with the addition of 2.0 mg of progesterone per millilitre for the active treatment (BHR‐100, Fresenius Kabi)". (p 2469) Comment: probably done |
| Blinding (performance bias and detection bias) Subjective outcome | Low risk | Quote: "Double blind" "The study drugs (progesterone and placebo) were provided in 250‐ml bottles with identical appearance". (p 2469) Comment: probably done |
| Blinding (performance bias and detection bias) Mortality | Low risk | Obtained from medical records; review authors do not believe this introduced bias. |
| Incomplete outcome data (attrition bias) Mortality | Low risk | A total of 31 participants (17 in the progesterone group and 14 in the placebo group) were lost to follow‐up. Missing outcome data were balanced in numbers between the progesterone group and the placebo group. |
| Incomplete outcome data (attrition bias) Favorable outcome | Low risk | A total of 31 participants (17 in the progesterone group and 14 in the placebo group) were lost to follow‐up. Missing outcome data were balanced in numbers between the progesterone group and the placebo group. |
| Selective reporting (reporting bias) | Low risk | The protocol for this trial was presented in Clinicaltrials.gov. It was clear that the published report included all expected outcomes. |
| Other bias | Unclear risk | This multicentre RCT was conducted in approximately 100 centres in 21 countries. The number of outcome events in each centre was quite low. We assessed potential bias for variation between‐centres as unclear because of factors such as different levels of expertise in treating TBI and outcome assessment. |