CiRUS: Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Recruiting

CT.gov ID

NCT04021381

Collaborator

(none)

262

Enrollment

Location

Arms

20.2

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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 renal 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

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: Some sites, according to their usual practice, may admit their patients to hospital the day before the surgery (D-1)), 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 within 7 days following F-URS, and 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 Design

Study Type:

Interventional

Anticipated 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

Actual Study Start Date :

Sep 25, 2020

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

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 Names: Lithos
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.

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 Names:

Lithos

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.

Outcome Measures

Primary Outcome Measures

Stone-free result [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.

Secondary Outcome Measures

SFR score 2, 3 and 4 [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 [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 [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. Mean USSQ (ureteral stone symptom questionnaire) score in each group.
To evaluate the compliance of potassium and magnesium citrate as assessed by citraturia [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 [3 months]
24-hour and fasting pH at 3 months.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years old
Efficient contraceptive method in women of childbearing age
At least one renal urolithiasis 10 ≤ size ≤ 20 mm
No recent ureterorenoscopy (< 6 months)
Planned flexible ureterorenoscopy procedure with holmium-laser dusting
CT-scan performed within 3 months before surgery
Affiliation to a social security regime
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)
Obstructive urinary tract malformation Cacchi-Ricci disease, Horseshoe kidney
Chronic renal failure (eGFR<30 ml/min/1.73m²)
Ongoing renal colic (within 7 days)
Untreated urinary tract infection (within 7 days)
Contraindications to ureterorenoscopy: coagulation disorders, high anesthetic risk
Contraindications to potassium and magnesium citrate: known hyperkalemia, known hypermagnesemia, uncontrolled diabetes, acute dehydration
Pregnant or breastfeeding women
Patient deprived of liberty or under legal protection measure (tutorship or curatorship);
Participation in another therapeutic trial