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SUSPEND Trial | Tamsulosin for Kidney Stones Explained · This Is Why with Dr. Busti

• 0:00
  SPEAKER_00: Okay, a patient comes into the emergency department with classic renal colic.
• 0:05
  SPEAKER_00: You do a CT scan, it shows a 4 millimeter distal uretal stone.
• 0:12
  SPEAKER_00: The pain is controlled, kidney function is okay, there's no fever, and you're planning to send the patient home.
• 0:19
  SPEAKER_00: So the question becomes: should we prescribe tamsellosin?
• 0:25
  SPEAKER_00: For years, many of us would have said yes, almost reflexively.
• 0:31
  SPEAKER_00: It relaxes the ureter, it helps the stone pass, and maybe prevents a procedure.
• 0:36
  SPEAKER_00: That was the idea behind medical expulsive therapy or MET.
• 0:42
  SPEAKER_00: But then came the suspend trial, a large UK study that seemed to say not so fast, right?
• 0:51
  SPEAKER_00: But like most landmark trials, the lesson isn't simply use it, don't use it.
• 0:58
  SPEAKER_00: The real lesson is understanding which patient, which stone, and which outcome we actually care about.
• 1:08
  SPEAKER_00: And with that, I'm Dr.
• 1:09
  SPEAKER_00: Busdy, your host on This Is Why, where we take medical knowledge from what to why, so that we can meaningfully impact how we practice medicine and healthcare.
• 1:23
  SPEAKER_00: In this series on landmark clinical trials, we'll explore practice-changing studies within the context of the broader overall evidence so that we can better understand how and why they apply in real-world clinical practice.
• 1:41
  SPEAKER_00: This isn't meant to be, guys, an exhaustive journal club.
• 1:46
  SPEAKER_00: Instead, my goal is to distill each study to its essentials and place it into the proper context so that we better understand why we do what we do.
• 1:59
  SPEAKER_00: Okay?
• 2:00
  SPEAKER_00: Now let me set this up.
• 2:02
  SPEAKER_00: Why this trial was needed, right?
• 2:06
  SPEAKER_00: Let's start with the clinical problem.
• 2:08
  SPEAKER_00: Most uretal stones are managed conservatively if the patient is stable, which means we've got pain control, control of nausea vomiting, there's no obvious infection, or threatening obstruction to the kidney, and we have the ability to arrange for follow-up.
• 2:31
  SPEAKER_00: The question is about adding a medication that can help stones pass and prevent the patient from needing a procedure.
• 2:40
  SPEAKER_00: Now, before the suspend trial, smaller studies and meta-analysis suggested that alpha blockers like Tamsellosin, calcium channel blockers like nifetapine might help.
• 2:55
  SPEAKER_00: I mean, think about it, the mechanism of action actually makes sense.
• 3:00
  SPEAKER_00: Alpha blockers may reduce that uretal smooth muscle tone and spasms that can occur from inflammation, particularly in that distal aspect of the ureter.
• 3:15
  SPEAKER_00: But the evidence had important problems.
• 3:18
  SPEAKER_00: There were small trials, variable inclusion criteria, inconsistent outcomes, and some uncertainty about whether the benefit applied broadly or only to certain renal stones.
• 3:34
  SPEAKER_00: So the suspend trial asked a very practical question.
• 3:40
  SPEAKER_00: In the real-world practice environment, if adults with uretal stones are managed expectantly, does giving TAMsilocin or niphetopine actually reduce the need for an intervention?
• 3:56
  SPEAKER_00: Okay.
• 3:57
  SPEAKER_00: So let's start to break down the study.
• 4:00
  SPEAKER_00: The suspend trial was a multi-center, randomized, double-blind, placebo-controlled, pragmatic trial that was conducted at 24 UK NHS hospitals.
• 4:16
  SPEAKER_00: Now the investigators enrolled adults 18 to 65 years of age who had uretal colic and a single CT confirmed uretal stone that was less than or equal to 10 millimeters or less than or equal to 1 centimeter.
• 4:40
  SPEAKER_00: Now, importantly, these were patients considered appropriate for conservative management, like I talked about at the beginning.
• 4:48
  SPEAKER_00: So this does not apply to the patient with sepsis from obstructed systems, uncontrolled pain, impaired renal function, okay, or a stone that clearly needs urgent urologic management.
• 5:05
  SPEAKER_00: Now, the patients were randomized to one of three groups: Tamselocin 400 micrograms or 0.4 milligrams daily, nifhetopine 30 milligrams daily, or the third group placebo, and they were to be treated for up to four weeks.
• 5:26
  SPEAKER_00: Randomized was balanced by the center, stone size, and stone location.
• 5:34
  SPEAKER_00: Now, here's the key design feature of the listen.
• 5:38
  SPEAKER_00: The primary outcome was not did the stone disappear on a repeat CT.
• 5:46
  SPEAKER_00: The primary outcome was whether the patient needed no further intervention to facilitate that stone's passage within a four-week period.
• 5:57
  SPEAKER_00: And that matters.
• 5:59
  SPEAKER_00: I mean, think about it this way, guys.
• 6:01
  SPEAKER_00: From a pragmatic standpoint, did the patient avoid a procedure?
• 6:07
  SPEAKER_00: That's actually a meaningful outcome.
• 6:09
  SPEAKER_00: I mean, patients care about avoiding uroscopies, stents, lithotripsies, hospital visits, and obviously more pain.
• 6:18
  SPEAKER_00: Okay?
• 6:20
  SPEAKER_00: Health systems care about avoiding procedures, cost, but from a biologic standpoint, that end is a also a proxy, right?
• 6:29
  SPEAKER_00: A patient could still have a stone, think about it, and not undergo an intervention within four weeks.
• 6:37
  SPEAKER_00: A patient's likelihood of intervention could depend on that patient's environment, their local practice of the provider's imaging habits, the urologist's level of threshold clinically, or even the patient's own preferences.
• 6:54
  SPEAKER_00: So the endpoint is clinically meaningful, but it is not the same as a confirmed stone passage, is it?
• 7:02
  SPEAKER_00: And this is one of those important nuances of this trial.
• 7:07
  SPEAKER_00: So what did they find?
• 7:09
  SPEAKER_00: Well, the suspend trial randomized a total of 1,167 patients, 1,136 were included in the primary analysis.
• 7:20
  SPEAKER_00: And the results were striking because all three groups literally looked almost the same.
• 7:27
  SPEAKER_00: No further intervention was required in about 81% of the tamsilosin group, 80% of the niphetipine group, and 80% of the placebo group.
• 7:41
  SPEAKER_00: Now, for tampselocin compared to the placebo, the adjusted risk difference was only 1.3 percentage points, with a confidence interval basically crossing no benefit.
• 7:53
  SPEAKER_00: Niphetopene compared to placebo, the adjusted difference was only 0.5 percentage points.
• 7:59
  SPEAKER_00: So the practical result was in this broad population of adults with stones in the ureter that were less than or equal to 10 millimeters, management being expectantly, right, neither tamsulosin nor niphetipine reduced the need for further intervention.
• 8:20
  SPEAKER_00: What about those secondary outcomes?
• 8:23
  SPEAKER_00: Well, unfortunately, they didn't rescue the study.
• 8:27
  SPEAKER_00: There was no difference that was clear and obvious in pain, analgesic use, time-to-stone passage, or even quality of life.
• 8:36
  SPEAKER_00: Cost-effective analysis was also done and did not support either drug in this NHS setting.
• 8:44
  SPEAKER_00: Now, safety is also worth mentioning.
• 8:46
  SPEAKER_00: Serious adverse events were uncommon, but treatment discontinuation due to intolerable effects was definitely numerically higher with the active treatment, specifically niphetipine.
• 8:59
  SPEAKER_00: And non-serious adverse effects were not systematically collected, that matters, which limits how completely we can assess the overall tolerability.
• 9:10
  SPEAKER_00: So here's why this trial mattered.
• 9:15
  SPEAKER_00: Suspend trial challenged a habit.
• 9:18
  SPEAKER_00: Before this trial, many clinicians were prescribing medical expulsive therapy or MET broadly.
• 9:25
  SPEAKER_00: Small stones, big stones, proximal stones, distal stones, gift tonsilocin.
• 9:31
  SPEAKER_00: We hope it helps.
• 9:33
  SPEAKER_00: Suspend said that approach is probably too broad.
• 9:36
  SPEAKER_00: But we need to also pause at that point, right?
• 9:39
  SPEAKER_00: The correct interpretation is not Tamsilocin never helps stones pass.
• 9:47
  SPEAKER_00: The better interpretation is in a broad, pragmatic population dominated by small stones, that routine MET did not reduce the need for an intervention.
• 10:00
  SPEAKER_00: And that distinction is everything.
• 10:03
  SPEAKER_00: Right?
• 10:04
  SPEAKER_00: Why?
• 10:05
  SPEAKER_00: Because about three-quarters of the stones found in the suspend trial were equal to or less than five millimeters.
• 10:13
  SPEAKER_00: And the mean stone size was 4.5 to 4.6 millimeters.
• 10:18
  SPEAKER_00: Many of those stones were likely to pass or at least avoid an intervention without any drug.
• 10:25
  SPEAKER_00: So if the placebo group already had an 80% no intervention rate, there's not much room for a medication to show a benefit, is there?
• 10:36
  SPEAKER_00: And this is called a ceiling effect problem.
• 10:40
  SPEAKER_00: If most patients do well anyway, a drug may look ineffective in the overall population, even if it helps a smaller, higher risk subgroup.
• 10:53
  SPEAKER_00: That is why later evidence became so important.
• 10:58
  SPEAKER_00: What later studies added to the suspend environment is several clarifications to the overall picture of application.
• 11:09
  SPEAKER_00: The furric trial published in the annals of emergency medicine enrolled patients with distal uretal stones, again, less than or equal to 10 millimeters, and they use CT confirmed passage at 28 days.
• 11:23
  SPEAKER_00: Again, overall tamsilocin did not significantly improve passage.
• 11:28
  SPEAKER_00: But in the pre-specified subgroup of patients with 5 to 10 millimeter stones, passage of those stones was higher with tamsilosin.
• 11:39
  SPEAKER_00: 83% versus 61%.
• 11:44
  SPEAKER_00: That gave a number needed to treat of 4.5.
• 11:49
  SPEAKER_00: Then there was the stone trial published in JAMA internal medicine that found also no significant benefit of tamsilocin for symptomatic uretal stones less than 9 millimeters in a United States emergency department population.
• 12:07
  SPEAKER_00: But again, the mean stone size was only 3.8 millimeters.
• 12:13
  SPEAKER_00: So this was another population with many stones that were probably going to pass without much help anyway.
• 12:21
  SPEAKER_00: All right, we moved on to a large Chinese multi-center trial that found TAMSLOCIN improved CT conformation expulsion of a distal urinal stone overall, but that benefit was driven by stones, listen, greater than five millimeters.
• 12:39
  SPEAKER_00: There was no real benefit with stones equal to or less than five millimeters.
• 12:44
  SPEAKER_00: And then there's the 2018 Cochrane review, which reached kind of a middle, similar middle ground.
• 12:51
  SPEAKER_00: Alpha blockers probably increased stone clearance overall, but the benefit appears much greater for stones over five millimeters than those equal to or less than five millimeters.
• 13:04
  SPEAKER_00: So the evidence after the suspend trial did not simply overturn the trial, it refined the overall question.
• 13:13
  SPEAKER_00: So the question is not, does tampselocin work for uretal stones?
• 13:18
  SPEAKER_00: The question should really be: does Tamselocin meaningfully help this specific patient with this type of specific stone size at this location and justify me prescribing it?
• 13:31
  SPEAKER_00: Now, if we look at guidelines in its context and current specialty guidance, they largely reflect that nuance.
• 13:39
  SPEAKER_00: The European Association of Urology acknowledges that the evidence is contradictory, especially when comparing with meta-analysis and a large placebo-controlled trials.
• 13:52
  SPEAKER_00: But the EAU concluded that the greatest benefit does appear to be in the distal uretal stones over 5 millimeters.
• 14:00
  SPEAKER_00: And they do recommend alpha blockers as one treatment option in that setting, noting that this is an off-label use.
• 14:18
  SPEAKER_00: Okay, in size.
• 14:20
  SPEAKER_00: Now, importantly, NICE specifically notes that practice did change after the suspend trial, but after reviewing the broader totality of the evidence, including these newer studies, the committee concluded that alpha blockers can help selected patients.
• 14:38
  SPEAKER_00: The AAUA position is also generally favorable towards alpha blocker MET for, again, appropriately selected patients with distal stones less than 10 millimeters, and more conditional for middle or proximal stones.
• 14:55
  SPEAKER_00: What about the emergency medicine commentaries and environment?
• 14:59
  SPEAKER_00: Well, they tend to be slightly more skeptical, especially because the emergency department clinicians see many small stones, okay, and need therapies that improve patient-oriented outcomes in a broad, undifferentiated population.
• 15:14
  SPEAKER_00: That skepticism then from that group makes sense, right?
• 15:18
  SPEAKER_00: I work in the emergency department, I say I've seen it, heard it.
• 15:21
  SPEAKER_00: So in most emergency departments where we see stones, they're small.
• 15:26
  SPEAKER_00: Most of them are going to pass spontaneously, and routine tamsilocin for everyone can be sometimes hard to justify.
• 15:35
  SPEAKER_00: The primary care, internal medicine, summaries and environment tend to land in a similar practical place.
• 15:42
  SPEAKER_00: Tamsilocin seems to most to be defensible for that 5 to 10 millimeter distal stone, not for tiny stones, they're likely going to pass anyway.
• 15:51
  SPEAKER_00: So, how do we apply this at the bedside?
• 15:54
  SPEAKER_00: Now we think about the real patient in front of us because we should take the evidence and apply it.
• 16:00
  SPEAKER_00: The process of EBM.
• 16:02
  SPEAKER_00: First, ask Is this patient safe for conservative management?
• 16:06
  SPEAKER_00: If there's fever, sepsis, infected obstruction, acute kidney injury, a solitary kidney with obstruction, right?
• 16:26
  SPEAKER_00: This is a urology, drainage, admission, a closer monitoring, and depending on the scenario, right?
• 16:31
  SPEAKER_00: Second, ask what is the stone's size?
• 16:36
  SPEAKER_00: If the stone is less than or equal to five millimeters, especially if distal, the probability of spontaneous passage is already high.
• 16:46
  SPEAKER_00: The incremental benefit of TAMsillosin is probably pretty small.
• 16:52
  SPEAKER_00: In that patient, the most important interventions are pain control, nausea control, hydration, guidance, return precautions, and follow-up.
• 17:04
  SPEAKER_00: Third, ask where is that stone?
• 17:07
  SPEAKER_00: If the stone is distal and greater than 5 millimeters and up to 10 millimeters, that is the patient who's most likely going to benefit from the alpha blocker.
• 17:18
  SPEAKER_00: And in that case, tamsilocin is reasonable to discuss with counseling that the benefit is not guaranteed.
• 17:25
  SPEAKER_00: The use may be off-label, and depending on the jurisdiction or where you practice, and uh patients may also experience adverse effects such as dizziness and orthostasis can sometimes occur.
• 17:36
  SPEAKER_00: All those things matter.
• 17:38
  SPEAKER_00: Now, lastly, don't use suspend to justify nifetapene.
• 17:45
  SPEAKER_00: Modern practice and guidelines have largely focused on alpha blockers rather than calcium channel blockers for medical expulsive therapy.
• 17:53
  SPEAKER_00: The practice takeaway is this suspend trial did not kill expulsive therapies, right?
• 17:58
  SPEAKER_00: It killed the idea that every uncomplicated uretal stone automatically needs it.
• 18:04
  SPEAKER_00: For small tones, especially less than five, focus on supportive care and follow-up.
• 18:09
  SPEAKER_00: For larger distal stones, between that five and ten millimeters, alpha blocker therapy remains reasonable, guideline-supported option when the patient is stable and appropriate for outpatient observation.
• 18:21
  SPEAKER_00: So that's the trial in context.
• 18:23
  SPEAKER_00: And on this is why my goal is to move us beyond what the data just simply shows to understand why it matters so that we can apply it more effectively to our clinical practices.
• 18:36
  SPEAKER_00: If you'd like a deeper breakdown, you can download the clinical trial handout that we put together for you, outlining the study framework and those key outcomes.
• 18:45
  SPEAKER_00: You can click on the link provided to you in the description of the episode on our podcast or through on YouTube.
• 18:52
  SPEAKER_00: Okay, and it'll take you to thisiswhy.
• 18:58
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• 19:07
  SPEAKER_00: Thanks so much for joining.
• 19:08
  SPEAKER_00: We'll see you next time.