Ureteral Calculi
Conditions
Keywords
Adrenergic alpha antagonists, drug therapy, tamsulosin, ureter
Brief summary
Current therapeutic options for ureteral stones include active intervention as well as conservative watch and wait approaches. Endoscopic treatment of ureteral stones has a high success rate and reliably results in immediate stone removal However, surgical as well as anaesthetic risks are not negligible and serious complications are possible. For many patients, a conservative treatment is an appealing option. Watchful waiting, however, not always results in stone clearance and may be associated with recurrent renal colics. The therapeutic potential of alpha-blockers for ureteral stone disease has been investigated prompted by the detection of alpha-receptors in ureteral smooth muscle cells. Blocking of such receptors, which are predominantly located in the distal part of the ureter results in relaxation of the ureteral wall and modulation of peristaltic activity. This mechanism has been proposed to facilitate stone passage for ureteral calculi. Numerous clinical trials have revealed a significant improvement of the stone expulsion rate using the alpha-blocker tamsulosin. Most of these studies were randomised but none were performed in a double-blind and placebo-controlled fashion. Therefore, the objective of this trial was to evaluate the efficacy of medical expulsive therapy with tamsulosin in a randomised, double-blind, placebo-controlled setting.
Interventions
DRUGTamsulosin
0.4 mg Tamsulosin once daily for 21 days
DRUGPlacebo
One placebo pill per day for 21 days or until stone expulsion
Sponsors
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients with a single 2 to 7mm ureteral stone below the common iliac vessels
Exclusion criteria
* presence of multiple ureteral stones * renal insufficiency (glomerular filtration rate below 60 ml/min) * urinary tract infection * a solitary kidney * pregnancy * history of ureteral surgery or previous endoscopic procedure * hypersensitivity to tamsulosin * current alpha-blocker, calcium-antagonist or corticosteroid medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stone Expulsion | 21 days | The primary end point was the number of patients per group experiencing stone expulsion until day 21, as confirmed by low-dose abdominal computed tomography (CT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Stone Passage | 21 days | The patient-defined time of stone expulsion was considered the event for time to stone passage. Patients with unnoticed stone expulsion were censored at the date of last positive stone status, and those who discontinued the therapy were censored at the date of last medication intake. Kaplan-Meier estimates were computed for time to stone passage. |
| Required Analgesics | Until stone expulsion or up to 21 days | Oral diclophenac (up to 3x50 mg pills) as first-line and oral metamizole (up to 8x 500mg pills)as second-line on-demand analgesics were prescribed. All patients were requested to record the required amount of pills per day |
| Maximum Daily Pain Score | Until stone expulsion or up to 21 days | All patients kept a diary to record the score of every painful episode on a 10-cm visual analogue scale (0= no pain at all; 10= strongest pain one can imagine). |
| Number of Participants Requiring Active Treatment | 21 days | The number of participants requiring active treatment was recorded. Shock wave lithotrypsy (SWL), ureterorenoscopy (URS) or insertion of an ureteral catheter were considered as active treatment. |
Countries
Switzerland
Participant flow
Recruitment details
Randomisation of 100 pts between 09.2006 and 09.2008 in a University Hospital
Pre-assignment details
10 patients were excluded from the final analysis due to stone expulsion before medication intake or withdrew of consent
Participants by arm
| Arm | Count |
|---|---|
| Tamsulosin Treatment Patients received one pill of Tamsulosin 400 micrograms once daily | 50 |
| Placebo Treatment Patients received Placebo pill once daily | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Stone expulsion before first medication | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo Treatment | Tamsulosin Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 48 Participants | 93 Participants |
| Age Continuous | 43.4 years STANDARD_DEVIATION 13.9 | 38.2 years STANDARD_DEVIATION 12.7 | 40.8 years STANDARD_DEVIATION 13.5 |
| Region of Enrollment Switzerland | 50 participants | 50 participants | 100 participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 39 Participants | 42 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 45 | 1 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 |
Outcome results
Primary
Number of Participants With Stone Expulsion
The primary end point was the number of patients per group experiencing stone expulsion until day 21, as confirmed by low-dose abdominal computed tomography (CT).
Time frame: 21 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamsulosin Treatment | Number of Participants With Stone Expulsion | 39 Participants |
| Placebo Treatment | Number of Participants With Stone Expulsion | 40 Participants |
Secondary
Maximum Daily Pain Score
All patients kept a diary to record the score of every painful episode on a 10-cm visual analogue scale (0= no pain at all; 10= strongest pain one can imagine).
Time frame: Until stone expulsion or up to 21 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamsulosin Treatment | Maximum Daily Pain Score | 3 Units on a scale |
| Placebo Treatment | Maximum Daily Pain Score | 7 Units on a scale |
Secondary
Number of Participants Requiring Active Treatment
The number of participants requiring active treatment was recorded. Shock wave lithotrypsy (SWL), ureterorenoscopy (URS) or insertion of an ureteral catheter were considered as active treatment.
Time frame: 21 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamsulosin Treatment | Number of Participants Requiring Active Treatment | 6 participants |
| Placebo Treatment | Number of Participants Requiring Active Treatment | 4 participants |
Secondary
Required Analgesics
Oral diclophenac (up to 3x50 mg pills) as first-line and oral metamizole (up to 8x 500mg pills)as second-line on-demand analgesics were prescribed. All patients were requested to record the required amount of pills per day
Time frame: Until stone expulsion or up to 21 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamsulosin Treatment | Required Analgesics | 3 pills per day |
| Placebo Treatment | Required Analgesics | 7 pills per day |
Secondary
Time to Stone Passage
The patient-defined time of stone expulsion was considered the event for time to stone passage. Patients with unnoticed stone expulsion were censored at the date of last positive stone status, and those who discontinued the therapy were censored at the date of last medication intake. Kaplan-Meier estimates were computed for time to stone passage.
Time frame: 21 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamsulosin Treatment | Time to Stone Passage | 7 days |
| Placebo Treatment | Time to Stone Passage | 10 days |