SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

Background Renal colic is the pain experienced by a patient when a renal calculus (kidney stone) causes partial or complete obstruction of part of the renal outflow tract. The standard analgesic regimes for renal colic are often ineffective; in some studies, less than half of patients achieve complete pain relief, and a large proportion of patients require rescue analgesia within 4 h. Current analgesic regimes are also associated with significant side effects including nausea, vomiting, drowsiness and respiratory depression. It has been hypothesised that beta adrenoreceptor agonists, such as salbutamol, may reduce the pain of renal colic. They have been shown to impact a number of factors that target the physiological causes of pain in renal colic (ureteric spasm and increased peristalsis, increased pressure at the renal pelvis and prostaglandin release with inflammation). There is biological plausibility and a body of evidence sufficient to suggest that this novel treatment for the pain of renal colic should be taken to a phase II clinical trial. The aim of this trial is to test whether salbutamol is an efficacious analgesic adjunct when added to the standard analgesic regime for patients presenting to the ED with subsequently confirmed renal colic. Methods A phase II, randomised, placebo-controlled trial will be performed in an acute NHS Trust in the East Midlands. Patients presenting to the emergency department with pain requiring IV analgesia and working diagnosis of renal colic will be randomised to receive standard analgesia ± a single intravenous injection of Salbutamol. Secondary study objectives will explore the feasibility of conducting a larger, phase III trial. Discussion The trial will provide important information about the efficacy of salbutamol as an analgesic adjunct in renal colic. It will also guide the development of a definitive phase III trial to test the cost and clinical effectiveness of salbutamol as an analgesic adjunct in renal colic. Salbutamol benefits from widespread use across the health service for multiple indications, extensive staff familiarity and a good side effect profile; therefore, its potential use for pain relief may have significant benefits for patient care. Trial registration ISRCTN Registry ISRCTN14552440. Registered on 22 July 2019

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