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Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi (CiRUS)
The prevalence of urolithiasis is around 10 % in the French population. It is thus a major public health issue. When the stone is not spontaneously removed, interventions such as extracorporeal lithotripsy or flexible ureteroscopy (F-URS) are performed. F-URS is usually preferred in inferior calyx stones > 7 mm in comparison with lithotripsy, with better results. Efficacy of ureteroscopy is based on the "stone-free rate" (SFR) at 3 months. A SFR index is assessed according to the existence of residual fragments and their size. SFR score 1 (fragment ≤ 1mm) has been poorly studied, and is supposed to occur in 60% of cases. These residual fragments account for the high frequency of recurrence, probably favored by crystals aggregation and growth of these fragments under supersaturated urines.
Indeed, calcium stones risk factors are urine supersaturation and crystal growth inhibitors deficiency. Citrate is the major crystal growth inhibitor in human urine. A hypocitraturia is reported in half of the lithiasic population.
Consequently, citrate salts appear as an interesting therapeutic option, in order to slow crystal growth but also to chelate calcium, and consequently to solubilize stones in situ. However, to date, there is no available controlled study after surgical intervention such as flexible ureteroscopy.
The aim of the investigator's study is to evaluate the efficacy of a 3-month potassium and magnesium citrate treatment following ureteroscopy on the elimination of residual fragments (SFR score 1).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Urolithiasis Calyx; Calculus | Dietary Supplement: Potassium and magnesium citrate Dietary Supplement: Placebo | Phase 3 |
The screening visit takes place 3 months to 3 days before the baseline visit. Patient will be informed of the study protocol by the surgeon who will perform the flexible ureteroscopy. As usual in clinical practice, a CT scan will be routinely performed. CT-scan interpretation will be centralized and performed blindly.
At the ureteroscopy day (baseline visit), inclusion and exclusion criteria will be checked by the surgeon. A second information on the study protocol will be given and the protocol consent will be signed.
The day of hospital admission, blood and urine will be collected by a nurse in order to define stone risk factors and other comorbidities after informed consent of the patients. Then patients will undergo ureteroscopy.
Stone fragments will be sent for analysis to the stone centre Laboratory (Tenon Hospital, Paris) with images of the stones during surgery (morphoconstitutional analysis).
Patients will be randomized for treatment after F-URS when they leave recovery room before discharge, after verification of randomization criteria. If the randomisation criteria are not completed, the patient will end its participation to the study.
Else, the patient is randomized and treatment for 3 months (placebo or citrate salts, blinded) will be delivered by the investigational site and administration will begin the day following surgery, thus discharge. A 33 cl glass will be provided for the administration of the treatment. Furthermore 24-hour urine collection will be explained and patients will be given the vessel in order to collect urine at M3 visit.
The end of study visit will take place at 3 months +/- 10 days after ureteroscopy visit.
Medical check-up by the urologist in charge, including a CT-scan and blood and urine biological tests under randomized treatment.
Randomized treatment will be stopped the day of this M3 visit. Adverse events (including drug tolerance, urinary symptoms) and date of stent removal if any will be collected. Compliance will be assessed, using a log book.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 262 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi: a Randomized Placebo Controlled Trial |
| Estimated Study Start Date : | July 2019 |
| Estimated Primary Completion Date : | October 2019 |
| Estimated Study Completion Date : | July 2021 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Potassium and magnesium citrate
Patients are treated with potassium and magnesium citrate
|
Dietary Supplement: Potassium and magnesium citrate
Patients are treated with potassium and magnesium citrate 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis.
Other Name: Lithos
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Placebo Comparator: Placebo
Patients are treated with placebo
|
Dietary Supplement: Placebo
Patient are treated with placebo 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis.
|
- Stone-free result [ Time Frame: 3 months ]Percentage of stone-free patients (SFR score 0 and 1) between the 2 groups at 3 months after ureteroscopy assessed by non-injected, low irradiation, thin slice CT-scan.
- SFR score 2, 3 and 4 [ Time Frame: 3 months ]Percentage of SFR score 2, 3 and 4 in the 2 groups at 3 months assessed by non-injected, low irradiation, thin slice CT-scan
- Urine supersaturation index [ Time Frame: 3 months ]Urine supersaturation index calculation based on the combination of urine pH, calciuria, phosphaturia, uricosuria, oxaluria) at 3 months in the two groups
- To evaluate the Safety of potassium and magnesium citrate: Percentage of patients with at least one adverse event throughout the study [ Time Frame: 3 months ]Percentage of patients with at least one adverse event throughout the study and collected at 3 months: epigastralgia, nausea, vomiting, bloating, constipation, diarrhea and urinary tract infection.
- To evaluate the compliance of potassium and magnesium citrate as assessed by citraturia [ Time Frame: 3 months ]24-hour and fasting citraturia (mmol/L) at 3 months.
- To evaluate the compliance of potassium and magnesium citrate as assessed by urinary pH [ Time Frame: 3 months ]24-hour and fasting pH at 3 months.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥18 years old
- At least one renal stone of the inferior calyx 12< size < 20 mm
- No recent ureterorenoscopy (< 6 months)
- Planned flexible ureteroscopy procedure with holmium-laser dusting
- CT-scan performed within 3 months before surgery
- Affiliation to a social security regime
- Agreement to sign informed consent
Exclusion Criteria:
- Stone density < 700 UH on pre-operative CT-scan
- History of infectious renal stones or monogenic lithiasic disease (cystinuria, primary hyperoxaluria)
- Urinary tract malformation, Cacchi-Ricci disease
- Chronic renal failure (eGFR < 30 ml/min/1.73m²)
- Ongoing renal colic (within 7 days)
- Untreated urinary tract infection (within 7 days)
- Contraindications to ureteroscopy: coagulation disorders, high anesthetic risk
- Contraindications to potassium and magnesium citrate : hyperkaliemia, hypermagnesemia
- Pregnant or breastfeeding women
- Patient deprived of liberty or under legal protection measure (tutorship or curatorship)
- Participation in another therapeutic trial
| Contact: Nathalie TABIBZADEH, MD | + 33 1 56 01 83 29 | nathalie.tabibzadeh@aphp.fr | |
| Contact: Jean-Philippe HAYMANN | +33 1 56 01 67 74 | jean-philippe.haymann@aphp.fr |
| France | |
| Department : Exploration fonctionnelles rénales, Centre de la lithiase Hôpital TENON | |
| Paris, France, 75020 | |
| Contact: Nathalie TABIBZADEH, MD + 33 1 56 01 83 29 nathalie.tabibzadeh@aphp.fr | |
| Contact: Jean-Philippe HAYMANN, PU-PH + 33 1 56 01 67 74 jean-philippe.haymann@aphp.fr | |
| Principal Investigator: | Nathalie TABIBZADEH, MD | Assistance Publique - Hôpitaux de Paris |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 24, 2019 | ||||||||
| First Posted Date ICMJE | July 16, 2019 | ||||||||
| Last Update Posted Date | July 16, 2019 | ||||||||
| Estimated Study Start Date ICMJE | July 2019 | ||||||||
| Estimated Primary Completion Date | October 2019 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Stone-free result [ Time Frame: 3 months ] Percentage of stone-free patients (SFR score 0 and 1) between the 2 groups at 3 months after ureteroscopy assessed by non-injected, low irradiation, thin slice CT-scan.
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | No Changes Posted | ||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi | ||||||||
| Official Title ICMJE | Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi: a Randomized Placebo Controlled Trial | ||||||||
| Brief Summary |
The prevalence of urolithiasis is around 10 % in the French population. It is thus a major public health issue. When the stone is not spontaneously removed, interventions such as extracorporeal lithotripsy or flexible ureteroscopy (F-URS) are performed. F-URS is usually preferred in inferior calyx stones > 7 mm in comparison with lithotripsy, with better results. Efficacy of ureteroscopy is based on the "stone-free rate" (SFR) at 3 months. A SFR index is assessed according to the existence of residual fragments and their size. SFR score 1 (fragment ≤ 1mm) has been poorly studied, and is supposed to occur in 60% of cases. These residual fragments account for the high frequency of recurrence, probably favored by crystals aggregation and growth of these fragments under supersaturated urines. Indeed, calcium stones risk factors are urine supersaturation and crystal growth inhibitors deficiency. Citrate is the major crystal growth inhibitor in human urine. A hypocitraturia is reported in half of the lithiasic population. Consequently, citrate salts appear as an interesting therapeutic option, in order to slow crystal growth but also to chelate calcium, and consequently to solubilize stones in situ. However, to date, there is no available controlled study after surgical intervention such as flexible ureteroscopy. The aim of the investigator's study is to evaluate the efficacy of a 3-month potassium and magnesium citrate treatment following ureteroscopy on the elimination of residual fragments (SFR score 1). |
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| Detailed Description |
The screening visit takes place 3 months to 3 days before the baseline visit. Patient will be informed of the study protocol by the surgeon who will perform the flexible ureteroscopy. As usual in clinical practice, a CT scan will be routinely performed. CT-scan interpretation will be centralized and performed blindly. At the ureteroscopy day (baseline visit), inclusion and exclusion criteria will be checked by the surgeon. A second information on the study protocol will be given and the protocol consent will be signed. The day of hospital admission, blood and urine will be collected by a nurse in order to define stone risk factors and other comorbidities after informed consent of the patients. Then patients will undergo ureteroscopy. Stone fragments will be sent for analysis to the stone centre Laboratory (Tenon Hospital, Paris) with images of the stones during surgery (morphoconstitutional analysis). Patients will be randomized for treatment after F-URS when they leave recovery room before discharge, after verification of randomization criteria. If the randomisation criteria are not completed, the patient will end its participation to the study. Else, the patient is randomized and treatment for 3 months (placebo or citrate salts, blinded) will be delivered by the investigational site and administration will begin the day following surgery, thus discharge. A 33 cl glass will be provided for the administration of the treatment. Furthermore 24-hour urine collection will be explained and patients will be given the vessel in order to collect urine at M3 visit. The end of study visit will take place at 3 months +/- 10 days after ureteroscopy visit. Medical check-up by the urologist in charge, including a CT-scan and blood and urine biological tests under randomized treatment. Randomized treatment will be stopped the day of this M3 visit. Adverse events (including drug tolerance, urinary symptoms) and date of stent removal if any will be collected. Compliance will be assessed, using a log book. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 3 | ||||||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Not yet recruiting | ||||||||
| Estimated Enrollment ICMJE |
262 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | July 2021 | ||||||||
| Estimated Primary Completion Date | October 2019 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | France | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT04021381 | ||||||||
| Other Study ID Numbers ICMJE | P170933J 2018-A03500-55 ( Other Identifier: ANSM ) |
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| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Assistance Publique - Hôpitaux de Paris | ||||||||
| Study Sponsor ICMJE | Assistance Publique - Hôpitaux de Paris | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE |
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| PRS Account | Assistance Publique - Hôpitaux de Paris | ||||||||
| Verification Date | July 2019 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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