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Randomised controlled trial
Tamsulosin and nifedipine did not improve stone passage over placebo nor were they cost-effective in ureteric stone disease
  1. Sayyid M Ammar Raza,
  2. Philip A Kalra
  1. Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK
  1. Correspondence to : Philip A Kalra, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK; Philip.kalra{at}srft.nhs.uk

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Commentary on: Pickard R, Starr K, MacLennan G, et al. Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial). Health Technol Assess 2015;19:1–172.

Context

Symptomatic ureteric stones are a common urological problem with an annual incidence of around 30/100 000 population in high-resource countries.1 Usually stones sized <6 mm pass spontaneously and are therefore managed conservatively. Recent European Association of Urology guidelines (August 2015) recommend the use of medical expulsion therapy (MET), in the form of α-blockers, to facilitate small stone passage.2 This guidance is primarily based on the findings of a meta-analysis in 2009 which assessed 47 clinical trials.3 Two classes of MET were assessed, calcium channel blockers and α blockers. Although the conclusion of this meta-analysis was that MET appeared to facilitate ureteric stone passage it also recognised several limitations. For example, the majority were unblinded, small, single-centre studies that had been developed without power calculations. There was also considerable heterogeneity between the trials, for example with several different drug preparations in the same class being used, differing durations of MET, different formulations and doses of METs, use of different adjunctive medications and also with stone size varying between the studies. For these reasons the need for a high quality, multicentre, adequately powered, placebo-controlled and blinded trial arose. These deficiencies and uncertainties underpinned the rationale for development of the SUSPEND trial.

Methods

The SUSPEND trial, funded by the National Institute for Health Research (NIHR) health technology assessment programme, was conducted to determine whether treatment with either tamsulosin 400 μg daily or nifedipine 30 mg daily for up to 4 weeks increased the rate of spontaneous stone passage versus placebo in patients presenting with acute ureteric nephrolithiasis. Participants were recruited from 24 National Health Service (NHS) hospitals over a 35-month period between January 2011 and December 2013. Adults (1167) aged 18–65 years-old were admitted as an emergency with a single ureteric stone of less than 10 mm diameter, as defined by CT. They were randomised 1:1:1 to take tamsulosin, nifedipine or placebo once daily. The primary outcome was the proportion of patients spontaneously passing a stone over 4 weeks. Tamsulosin and nifedipine cohorts were aggregated and compared to placebo for time to stone passage. Comparisons for this outcome were also made between the nifedipine and tamsulosin groups. Of the 1167, 975 participants were included in the primary outcome analysis (378/391 tamsulosin, 379/387 nifedipine, 379/399 placebo). The study was adequately powered and the target of 354 participants per study arm was achieved.

Findings

No difference in stone passage was found between combined MET (aggregated nifedipine and tamsulosin) and placebo (OR 1.04, 95% CI 0.77 to 1.43; absolute difference 0.8%, 95% CI −4.1% to 5.7%, p value 0.78). Additionally, no difference was found between the two active treatments, tamsulosin and nifedipine, (OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI −4.6% to 6.6%, p value 0.77). These findings remained unchanged despite adjusting for sex, stone size and stone location. There were also no statistically significant differences between the three cohorts in other secondary outcome measures such as pain control, number of unplanned interventions and excess admission days. Furthermore, there was no difference in quality-adjusted life years gained or in cost between the trial groups.

Commentary

The SUSPEND trial did not demonstrate any benefit in using tamsulosin or nifedipine in the treatment of ureteric stones of <10 mm diameter. Their utilisation would therefore not be cost-effective for use in the NHS. However, the robust design and size of the SUSPEND trial gives confidence that its results are reliable and definitive and these should now change practice. The trial result is at variance with the conclusion of the meta-analysis by Seitz et al,3 but as described above, that had major limitations particularly because of inclusion of heterogeneous study populations.

Implications for practice

There now appears to be no role for either α blockers or calcium channel antagonists as MET in patients presenting with symptomatic ureteric stones of <10 mm diameter and current guidelines on the medical management of ureteric stones should be re-evaluated.

References

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Footnotes

  • Correction notice This article has been corrected since it was published Online First. The order of the first and second authors has been transposed.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.