for the main comparison.
| Progesterone compared with no progesterone or placebo for traumatic brain injury | ||||||
|
Patient or population: people with acute TBI secondary to head injury Settings: hospitals, intensive care units Intervention: progesterone therapy Comparison: no progesterone or placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Progesterone | |||||
| Mortality at end of scheduled follow‐up | 192 per 1000 |
175 per 1000 (125 to 246) |
RR 0.91 (0.65 to 1.28) | 2376 (5 studies) | ⊕⊕⊝⊝ Low1,2,3 | There is no evidence of a reduction of mortality at the end of scheduled follow‐up as a result of progesterone therapy. Our confidence in this evidence is limited as we have assessed it as low quality. |
| Disability (unfavourable outcomes: death, vegetative state, severe disability; GOS 1‐3) at end of scheduled follow‐up | 533 per 1000 |
522 per 1000 (474 to 565) |
RR 0.98 (0.89 to 1.06) | 2260 (4 studies) |
⊕⊕⊕⊝ Moderate1,3 | There is no evidence of a difference in disability (unfavourable outcomes) at the end of scheduled follow‐up as a result of progesterone therapy. Our confidence in this evidence is somewhat limited as we have assessed it as moderate quality. |
| Intracranial pressure (ICP) within the treatment period | ‐ | ‐ | ‐ | 3 studies | ‐ | In Xiao 2008, ICP data were presented as mean values. In Wright 2006, ICP data were presented as the mean frequency of pressures exceeding threshold values. In Skolnick 2014, ICP data were presented as the population with increased ICP. We were therefore not able to perform meta‐analysis. There was no evidence that progesterone therapy has an effect on ICP. |
| Blood pressure | ‐ | ‐ | ‐ | 1 study | ‐ | "Throughout the three‐day infusion interval, there was no difference between the progesterone and placebo groups" (Wright 2006) |
| Body temperature | ‐ | ‐ | ‐ | 1 study | ‐ | "Progesterone group experienced a lower increase in mean temperature than the control group" (Wright 2006) |
| Adverse events | ‐ | ‐ | ‐ | 4 studies | ‐ | Wright 2014 reported that phlebitis or thrombophlebitis was significantly more frequent in the progesterone group than in the placebo group (882 cases, RR 3.03; 95% CI, 1.96 to 4.66). The rates of other serious and non‐serious adverse events were similar in the 4 studies. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval;GOS: Glasgow Outcome Scale; ICP: intracranial pressure; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | ||||||
1. We judged the overall risk of bias of two studies as high, and two studies as unclear. However, most data were from studies at low or unclear risk of bias, so we did not downgrade for risk of bias.
2. Downgraded once for inconsistency (substantial heterogeneity: I² = 62%, P value 0.03)
3. Downgraded once for inconsistency (the dosage, treatment routine and vehicles of progesterone varied across studies. Different time points were involved in the analysis of mortality and unfavourable outcomes).