Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: multicentre placebo controlled randomised trial of calcium channel blockers (nifedipine) and alpha blockers (tamsulosin) - The SUSPEND trial

Urinary stone disease is very common with an estimated prevalence among the general population of 2-3% and an estimated lifetime risk of 1 in 8 for white males and 5-6% for white females with males forming stones three times as often as females. Urinary stones often recur and the lifetime recurrence rate is approximately 50%. In recent years, a growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs which cause relaxation of ureteric smooth muscle can enhance the spontaneous passage of ureteric stones. The selective a-adrenergic antagonist, Tamsulosin has specificity for a-1A and a-1D receptor subtypes, whilst other a-blockers variably block all a-1 receptor sub-types in a non-specific manner. Similarly, calcium channel blockers such as Nifedipine inhibit ureteric smooth muscle contraction. The use of both classes of drugs in augmenting the passage of ureteric stones has been termed medical expulsive therapy (MET) and this is proposed as a way to enhance stone passage and avoid the need for further interventions. However, the majority of clinical trials conducted to date have been small and of poor to moderate quality in terms of trial methodology or design and have lacked a comprehensive economic evaluation. The SUSPEND trial will therefore investigate whether: 1) the use of MET will result in an absolute increase in the spontaneous stone passage rate of at least 25% compared with placebo and 2) the use of an alpha blocker (Tamsulosin) will result in an absolute increase of 10% in the spontaneous stone passage rate compared with a calcium channel blocker (Nifedipine). 1200 eligible and consented participants will be randomised to a unique blinded patient numbered pack containing 28 capsules (400 participants to each of the three treatment groups - alpha blocker, calcium channel blocker and placebo). Participants will take one capsule orally per day and will be followed-up by postal questionnaires sent from the co-ordinating office (CHaRT, Aberdeen) at four and 12 weeks after randomisation. Participants will be reviewed in clinic approximately four weeks after being randomised.