| Methods |
Multicentre study
Random allocation (identical sequentially numbered treatment boxes), blocked per centre
Double‐blind treatment: code broken after all events and outcomes had been recorded
ITT |
| Participants |
Clinical diagnosis of aneurysmal SAH verified on CT or in the CSF: if negative CT, angiography had to confirm an aneurysm before randomisation
Male:female: treatment group 89:140; placebo group 73:160
Mean age: treatment group 56 years; placebo group 55 years
Excluded: SAH > 96 hours or operation planned < 48 hours, coagulation disorders or thrombotic disease, renal failure, pregnancy, previous tranexamic acid treatment or people in whom death appeared imminent |
| Interventions |
Tranexamic acid (6 g per day iv in 6 doses in week 1, and 6 g orally per day in 4 doses in week 2 and 3) versus identical‐appearing placebo treatment for a maximum treatment duration of 3 weeks
All participants received standard anti‐ischaemic treatment with nimodipine and hypervolaemia |
| Outcomes |
Outcome: Glasgow Outcome Scale at 3 months
Events: rebleeding‐definite: confirmed by CT scan or at necropsy; rebleeding‐possible: sudden deterioration and death; infarction‐definite: confirmed by CT scan or at necropsy; infarction‐probable: gradual development of focal neurologic signs with or without deterioration in the level of consciousness; hydrocephalus: gradual deterioration of consciousness with on CT hydrocephalus and no other explanation
Postoperative ischaemia: deterioration of consciousness or development of focal neurological signs immediately after recovery from anaesthesia compared to preoperative status, without rebleeding, infarction or hydrocephalus on CT or at autopsy
Poor outcome caused by the initial bleeding: impaired consciousness or focal neurological signs from the time of the initial bleeding, without rebleeding, infarction or hydrocephalus on CT or at autopsy |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Sequence was generated by use of random number tables |
| Allocation concealment (selection bias) |
Low risk |
Identical, sequentially numbered treatment boxes, blocked per centre were used and boxes were consecutively numbered and administered in the same order to each following participant |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Identical and sequentially numbered treatment boxes were used |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
"Only after recording of all events and outcomes, the trial code was broken" |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
No missing data |
| Selective reporting (reporting bias) |
Low risk |
Previously published protocol |
| Other bias |
Low risk |
None suspected based on study design and outcome |
