Medical Expulsive Therapy Research Articles

Tamsulosin versus nifedipine for the management of lower ureteral stones: a meta-analysis

Objective To compare the efficacy and safety of tamsulosin with nifedipine for medical expulsive therapy (MET) in patients with lower ureteral stones (LUS). Methods Randomized controlled trials(RCTs)in comparison of tamsulosin and nifedipine in treatment of LUS published in Pubmed, Cochrane Library, Embase, CNKI, CBM, Wanfang and VIP from databases establishment to July 2015 were retrieved. According to Cochrane handbook, the quality of included RCTs were assessed, and the relevant data including the number of participants, stone size, stone expulsion rate, time to stone expulsion, drug-related side effect, the incidence of ESWL or ureteroscopy lithotripsy (URSL) after MET and analgesic dose were extracted by two reviewers independently. The statistical software RevMan 5.2 was used for meta-analysis with regard to the stone expulsion rate, the incidence of ESWL or URSL and adverse effects. This study lasted more than one month from June to July 2015. Results A total of 13 RCTs with 4 831 patients were eligible. The results showed that the stone expulsion rate and the incidence rate of ESWL or URSL after MET were 92%(2 221/2 423) and 8%(27/333) in the tamsulosin group, and 73%(1 748/2 408) and 20%(67/328) in the nifedipine group. There are statistically significant differences(RR=1.24, 95% CI 1.13-1.37, P<0.05; RR=0.40, 95% CI 0.27-0.60, P<0.05, respectively). The subgroup analysis indicated no statistically significant differences in drug-related adverse effects between tamsulosin and nifedipine with 5%(99/1 804)and 7% (117/1 796) minor adverse effects respectively and less than 1% severe adverse effects in both groups(RR=0.85, 95% CI 0.65-1.10, P=0.21; RR=0.49, 95% CI 0.09-2.59, P= 0.40). Conclusion Compared to nifedipine, tamsulosin has higher stone expulsion rate and lower incidence rates for ESWL or URSL. Since there was no obvious adverse effects, tamsulosin could be considered as a preferable option for patients with LUS. Key words: Tamsulosin; Nifedipine; Medical expulsive therapy; Ureteral stones; Meta-analysis

Author Reply

We appreciate the editorial drawing attention to one of the core assumptions of our original research question. We asked whether there were deleterious effects of allowing failure of medical expulsive therapy (MET) under the common assumption that stones might be “medically expelled.”

Role of Alfuzosin in Spontaneous Passage of Distal Ureteric Calculi

Medical expulsion therapy has been shown to be a useful adjunct to observation in the management of ureteral stones. Alpha-1-adrenergic receptor antagonists have been studied in this role. Alpha-1 receptors are located in the human ureter, especially the distal ureter. Alpha-blockers have been demonstrated to increase expulsion rates of distal ureteral stones, decrease time to expulsion, and decrease need for analgesia during stone passage. Alpha-blockers promote stone passage in patients receiving shock wave lithotripsy, and may be able to relieve ureteral stent-related symptoms. In the appropriate clinical scenario, the use of α-blockers is recommended in the conservative management of distal ureteral stones.

65 The role of nifedipine as medical expulsive therapy (MET) after extracorporeal shockwave lithotripsy (ESWL): A systematic review and meta-analysis

65 The role of nifedipine as medical expulsive therapy (MET) after extracorporeal shockwave lithotripsy (ESWL): A systematic review and meta-analysis

Unsuccessful Medical Expulsive Therapy: A Cost to Waiting?

To compare clinical outcomes between patients with ureteral stones who underwent an unsuccessful trial of medical expulsive therapy (MET) and patients who did not attempt MET. We reviewed the clinical records of all potential candidates for MET who were referred from the emergency department to a subspecialty stone clinic. Of 348 potential candidates, 133 patients (38%) went directly to surgery (NMET) and 215 patients (62%) initiated MET. In the latter group, MET was unsuccessful in 45 patients (21%) (UMET). Stone symptoms were the primary rationale for surgery in 20 (44%) UMET patients and 69 (52%) NMET patients. The UMET patients were more likely to be younger and have smaller, more distal stones than NMET patients. All stones were cleared by ureteroscopy. The average interval from stone clinic assessment to surgery was longer in the UMET patients (17 days) than in the NMET patients (1 day; P <.001). The UMET patients underwent more preoperative computed-tomography scans (2.1) than did the NMET patients (1; P <0.001). There were no differences between the 2 groups in the residual stone burden, pre- or postoperative repeat visits to the emergency department, or repeat surgery. In this population, we did not observe any detrimental impact of an unsuccessful trial of MET (beyond the additional time and imaging costs). If more confident and effective symptom control could be achieved, expansion of utilization and duration of MET may be a path to improved patient outcomes and cost control.

Efficacy and safety of silodosin in the medical expulsion therapy for distal ureteral calculi: a systematic review and meta-analysis.

Using a selective α-adrenoceptor blocker for medical expulsive therapy (MET) is an effective treatment approach widely used for ureteral stones. The aim of the review was to assess the efficacy and safety of silodosin in medical expulstion therapy compared with placebo and tamsulosin. A systematic search was performed in PubMed, Cochrane Library and Embase to identify randomized controlled trials that compared silodosin with a placebo or tamsulosin for ureteral calculi. Eight publications involving a total of 1048 patients were used in the analysis, which compared silodosin with placebo and tamsulosin. We found that silodosin was effective in treating ureteral calculi in our meta-analysis and was superior to tamsulosin in its efficacy. The expulsion rate of all ureteral stones (OR 1.59, 95% CI 1.08, 2.36, P = 0.02), the expulsion rate of distal ureteral stones (OR 2.82, 95% CI 1.70, 4.67, P < 0.0001) and the expulsion time (days) of distal ureteral stones (standard mean difference (SMD) -4.71, 95% CI -6.60, -2.83, P < 0.00001) indicated that silodosin was more effective than the placebo. Moreover, expulsion rate (OR 2.54, 95% CI 1.70, 3.78, P < 0.00001), expulsion time (days) (SMD -2.64, 95% CI -3.64, -1.64, P < 0.00001) and pain episodes (P < 0.00001) indicated that silodosin was more effective than the tamsulosin. Even though silodosin had a significant increase in abnormal ejaculation compared with tamsulosin, no significant differences were observed for complications (OR 1.00, 95% CI 0.58, 1.74, P = 1.00). This meta-analysis indicated that silodosin was superior to placebo or tamsulosin in the efficacy for distal ureteral calculi with better control of pain. The safety profile of silodosin was similar to tamsulosin though retrograde ejaculation was worse for silodosin use. We conclude that silodosin might have potential as a MET for ureteral stones.

Evaluating the Combination of Two Different Alpha-1 Blockers with One Phosphodiesterase-5 Inhibitor (PDE-5) as Medical Expulsive Therapy for Distal Ureteric Calculi

Journal of the American College of Surgeons: October 2015 - Volume 221 - Issue 4 - p S174-S175 doi: 10.1016/j.jamcollsurg.2015.07.416

E62 Effect of medical expulsive therapy on the health-related quality of life of patients with ureteral stones: A critical evaluation

E62 Effect of medical expulsive therapy on the health-related quality of life of patients with ureteral stones: A critical evaluation

Efficacy and Safety of Alfuzosin as Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis.

BackgroundAlfuzosin has been widely used to treat benign prostatic hyperplasia and prostatitis, and is claimed to be a selective agent for the lower urinary tract with low incidence of adverse side-effects and hypotensive changes. Recently, several randomized controlled trials have reported using Alfuzosin as an expulsive therapy of ureteral stones. Tamsulosin, another alpha blocker, has also been used as an agent for the expulsive therapy for ureteral stones. It is unclear whether alfuzosin has similar efficacy as Tamsulosin in the management of ureteral stones.ObjectiveTo perform a systematic review and analysis of literatures comparing Alfuzosin with Tamsulosin or standard conservative therapy for the treatment of ureteral stones less than 10 mm in diameter.MethodsA systematic literature review was performed in December 2014 using Pubmed, Embase, and the Cochrane library databases to identify relevant studies. All randomized and controlled trials were included. A subgroup analysis was performed comparing Alfuzosin with control therapy on the management of distal ureteral stones.ResultsAlfuzosin provided a significantly higher stone-free rate than the control treatments (RR: 1.85; 95% confidence interval [CI], 1.35–2.55; p<0.001), and a shorter stone expulsion time (Weighted mean difference [WMD]: -4.20 d, 95%CI, -6.19 to -2.21; p<0.001), but it has a higher complication rate (RR: 2.02; 95% CI, 1.30–3.15; p<0.01). When Alfuzosin was compared to Tamsulosin, there was no significant difference in terms of stone-free rate (RR: 0.90; 95% CI, 0.79–1.02; p = 0.09) as well as the stone expulsion time (WMD: 0.52 d, 95%CI, -1.61 to 2.64; p = 0.63). The adverse effects of Alfuzosin were similar to those of Tamsulosin (RR: 0.88; 95% CI, 0.61–1.26; p = 0.47).ConclusionsAlfuzosin is a safe and effective agent for the expulsive therapy of ureteral stones smaller than 10 mm in size. It is more effective than therapeutic regiment without alpha blocker. It is equivalent to Tamsulosin in its effectiveness and safety profile. Adverse effects should always be kept in mind when use this class of drugs.

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).

Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. Urology departments in 24 UK NHS hospitals. Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks. Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location. Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies. Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

Adjunctive medical expulsive therapy for kidney and ureteral stone fragments following shock wave lithotripsy

Reason for Withdrawal This review was withdrawn: authors had not progressed the review following protocol publication in 2011. To view the published versions of this article, please click the 'Other versions' tab.

Injuria renal aguda en ureterolitiasis unilateral en paciente no monorrenal

Introduction and objectivesBilateral ureterolithiasis commonly causes acute renal failure, but unilateral obstruction in the non-single kidney patient produces an increase in nitrogen compounds in only a percentage of cases, which ultimately end up requiring urinary tract bypass surgery. In urinary tract obstruction there are changes, including haemodynamic patterns and other factors that influence glomerular filtration rate and can lead to acute renal failure, even when there is unilateral ureterolithiasis with a healthy and unobstructed contralateral kidney. There are few data about the proportion of these patients who present with acute kidney injury. The aim of this study is to assess the relationship between unilateral ureterolithiasis in non-single kidney patients and acute kidney injury. Materials and methodsA cross-sectional, descriptive, retrospective study, was performed with a sample of 77 hospital patients diagnosed with unilateral ureterolithiasis during the period between October and December 2013. The characteristics of the sample and of ureterolithiasis were described. Calculations were made to obtain the prevalence of acute kidney injury and relating this to the level of hydronephrosis presented, urinary tract infection, and treatment. ResultsFrom the total sample (65 patients), 17 patients (26.2%) had acute kidney injury. Of these 17 patients with acute kidney injury majority (82.4%) were male, most with hydronephrosis grade3 (35.3%), 3 had concomitant urinary tract infection. More than half (58.8%) of cases of unilateral ureterolithiasis associated with acute kidney injury required medical expulsive therapy. ConclusionsAcute kidney injury secondary to unilateral ureterolithiasis in the non-single kidney patient is present in a significant percentage of patients, predominantly in men, and most cases of acute kidney injury are associated with a distal presentation of ureterolithiasis at the time of diagnosis. Given the distal character, and the average size of the stone, most ureterolithiasis even with acute kidney injury can be managed with medical expulsive therapy, and only some patients require renal drainage.

Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial

We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter. This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion. There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups. We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered.

SMS text pre-notification and delivery of reminder e-mails to increase response rates to postal questionnaires in the SUSPEND trial: a factorial design, randomised controlled trial.

BackgroundPatient-reported outcomes are vital in informing randomised controlled trials (RCTs) and health-care interventions and policies from the patient’s perspective. However, participant non-response may introduce bias and can affect the generalisability of the trial.This study evaluates two interventions aimed at increasing response rates to postal questionnaires within a large, UK-wide RCT: pre-notification via short messenger service (SMS) text prior to sending the initial mailing of trial questionnaires versus no pre-notification; for non-responders to the initial mailing of the questionnaires, an e-mail reminder (containing a hyperlink to complete the questionnaire online) versus a postal reminder.MethodsThis study is a 2×2 partial factorial design RCT nested within an RCT of medical expulsive therapy for ureteric stone disease. Participants who supplied a mobile telephone number were randomly assigned to receive an SMS text pre-notification of questionnaire delivery or no pre-notification. Those who supplied an e-mail address were randomly assigned to receive a questionnaire reminder by e-mail or post. Participants could be randomly assigned to the pre-notification comparison or the reminder comparison or both. The primary outcome measure was response rate at each questionnaire time point.ResultsFour hundred eighteen participants were randomly assigned to the SMS pre-notification comparison (80 % were male, and the mean age was 41 years with a standard deviation (SD) of 11.1). The intervention had no effect on response rate at either questionnaire time point. In subgroup analyses, SMS pre-notification increased response rates in women but only at the first questionnaire time point. One hundred nineteen participants were randomly assigned to the reminder comparison (80 % were male, and the mean age was 42 years with an SD of 12.1). There was no difference in response rate in those who received an e-mail reminder compared with those who received a postal reminder.ConclusionsSMS text pre-notification of questionnaire delivery and email delivery of questionnaire reminders did not improve response rates. There was some evidence to suggest that SMS text pre-notification may be effective in women, and further studies to investigate this may be warranted. E-mail reminders for participants to return their postal questionnaire could be advantageous given that response rates were similar following either type of reminder and the low cost of delivering an e-mail compared with a postal reminder.This is a substudy of the SUSPEND trial (ISCTRN69423238) (18 Nov. 2010).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0808-9) contains supplementary material, which is available to authorized users.

Perinatal Outcomes with Tamsulosin Therapy for Symptomatic Urolithiasis

Medical expulsive therapy represents an effective adjunctive treatment for nonpregnant patients with symptomatic urolithiasis. Tamsulosin is classified by the FDA (Food and Drug Administration) as a category B medication. However, to our knowledge no published data exist for human pregnancy. We explored the safety and efficacy of tamsulosin therapy for symptomatic urolithiasis occurring during pregnancy. We retrospectively identified patients treated with tamsulosin for stone disease during pregnancy at the Mayo Clinic during 2000 to 2014. This medical expulsive therapy cohort was matched 2:1 to pregnant women with symptomatic urolithiasis during pregnancy who did not receive medical expulsive therapy. Groups were compared using linear mixed models for continuous variables and exact conditional logistic regression models for nominal variables to take into account correlation due to matching. A total of 27 patients receiving medical expulsive therapy comprised the study cohort. Median duration of antepartum tamsulosin exposure was 3 days (range 1 to 110), occurring during the first, second and third trimester in 3 (11%), 11 (40.7%) and 18 (67%) patients, respectively. Mean gestational age at delivery was 38.1 weeks (SD 2.4) and 6 (22%) infants were born preterm. All infant birthweights were considered appropriate for gestational age, and no cases of spontaneous abortion, intrauterine demise or neonatal congenital anomalies were encountered. Comparison between the medical expulsive therapy and control groups demonstrated no significant differences in maternal or infant outcomes for any of the examined variables. Tamsulosin medical expulsive therapy does not appear to be associated with adverse maternal or fetal outcomes and may be considered as adjunctive therapy for urolithiasis during pregnancy.

Editorial Comment

The prevalence of urolithiasis in the United States has steadily increased over the past several years. 1 Scales Jr., C.D. Smith A.C. Hanley J.M. et al. Prevalence of kidney stones in the United States. Eur Urol. 2012; 62: 160 Abstract Full Text Full Text PDF PubMed Scopus (1468) Google Scholar The morbidity caused by stone disease is similarly significant, as 30% of patients diagnosed with stone disease report loss of work associated with the diagnosis. 2 Pearle M.S. Calhoun E.A. Curhan G.C. et al. Urologic diseases in America project: urolithiasis. J Urol. 2005; 173: 848 Abstract Full Text Full Text PDF PubMed Scopus (627) Google Scholar Furthermore, when medical expulsive therapy is unsuccessful, procedural intervention often presents a significant financial burden to both the patient and practice. 3 Tosoian J.J. Ludwig W. Sopko N. et al. The effect of repair costs on the profitability of a ureteroscopy program. J Endourol. 2015; 29: 406-409 Crossref PubMed Scopus (31) Google Scholar As such, and in light of health care reform with greater focus on financial responsibility, the potential therapeutic effect of lifestyle modifications such as diet and exercise remains an important consideration. 4 Hyams E.S. Matlaga B.R. Cost-effectiveness treatment strategies for stone disease for the practicing urologist. Urol Clin North Am. 2013; 40: 129 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar In the accompanying article, Doluoglu et al 5 Doluoglu O.G. Demirbas A. Kilinc M.F. et al. Can sexual intercourse be an alternative therapy for distal ureteral stones? A prospective, randomized, controlled study. Urology. 2015; 86: 19-24 Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar hypothesize that sexual intercourse may facilitate the passage of distal ureteral stones via a nitric oxide–mediated pathway. Specifically, the authors propose that nitric oxide released in high concentrations in cavernous tissue during erection and intercourse may be released in the distal ureter as well, triggering relaxation of ureteral muscle. Indeed, previous studies have identified nitrergic fibers in the distal ureter and demonstrated a relaxant effect of NO on ureteral smooth muscle. 6 Yucel S. Baskin L.S. Neuroanatomy of the ureterovesical junction: clinical implications. J Urol. 2003; 170: 945 Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar , 7 Iselin C.E. Ny L. Larsson B. et al. The nitric oxide synthase/nitric oxide and heme oxygenase/carbon monoxide pathways in the human ureter. Eur Urol. 1998; 33: 214 Crossref PubMed Scopus (26) Google Scholar Can Sexual Intercourse Be an Alternative Therapy for Distal Ureteral Stones? A Prospective, Randomized, Controlled StudyUrologyVol. 86Issue 1PreviewTo investigate the effect of sexual intercourse on spontaneous passage of distal ureteral stones. Full-Text PDF

Effect of medical expulsive therapy on the health-related quality of life of patients with ureteral stones: a critical evaluation.

To evaluate the possible effects of medical expulsive therapy (MET) on the health-related quality of life (HRQOL) of the patients under watchful waiting for ureteral stones. A total 120 patients with ureteral stones were included into this study program. Patients were divided into two subgroups. While patients in group 1 received medical therapy only for colic pain if needed, patients in group 2 received MET (tamsulosin 0.4 mg/once daily) in addition to medical therapy. All cases were evaluated weekly during 1-month period, and the patients with persistent stones after this period in both groups were evaluated with respect to the analgesic requirement, number of renal colic attacks as well as emergency department (ED) visits along with the QOL scores. Mean values of patient age and stone burden were 37.14 ± 2.46 years and 42.04 ± 2.03 mm(2), respectively. Evaluation of the cases with residing stones after 4 weeks (28 cases in group 1 and 27 cases in group 2) with or without MET revealed following findings; renal colic, total amount of analgesic required and the mean number of ED visits were significantly lower in cases receiving MET. Evaluation of the mean HRQOL in terms of EQ-5D index and EQ-5D VAS values in both groups again demonstrated higher mean values in patients undergoing MET (p < 0.05). Our findings indicated that MET for ureteral calculi during watchful waiting period could increase the HRQOL scores by lowering the number of both renal colic attacks and ED visits resulting in decreased analgesic need.

Re: Role of Tamsulosin, Tadalafil and Silodosin as the Medical Expulsive Therapy in Lower Ureteric Stone: A Randomized Trial (A Pilot Study)

Re: Role of Tamsulosin, Tadalafil and Silodosin as the Medical Expulsive Therapy in Lower Ureteric Stone: A Randomized Trial (A Pilot Study)

Stones: Now the drugs don't work: tamsulosin is ineffective as medical expulsive therapy.

Stones: Now the drugs don't work: tamsulosin is ineffective as medical expulsive therapy.

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial

Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. UK National Institute for Health Research Health Technology Assessment Programme.