Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi: a Randomized Placebo Controlled Trial

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

Sponsors

Lead sponsor: Assistance Publique - Hôpitaux de Paris

Source Assistance Publique - Hôpitaux de Paris
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).

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.

Overall Status Not yet recruiting
Start Date July 2019
Completion Date July 2021
Primary Completion Date October 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Stone-free result 3 months
Secondary Outcome
Measure Time Frame
SFR score 2, 3 and 4 3 months
Urine supersaturation index 3 months
To evaluate the Safety of potassium and magnesium citrate: Percentage of patients with at least one adverse event throughout the study 3 months
To evaluate the compliance of potassium and magnesium citrate as assessed by citraturia 3 months
To evaluate the compliance of potassium and magnesium citrate as assessed by urinary pH 3 months
Enrollment 262
Condition
Intervention

Intervention type: Dietary Supplement

Intervention name: Potassium and magnesium citrate

Description: Patients are treated with potassium and magnesium citrate 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis.

Arm group label: Potassium and magnesium citrate

Other name: Lithos

Intervention type: Dietary Supplement

Intervention name: Placebo

Description: Patient are treated with placebo 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis.

Arm group label: Placebo

Eligibility

Criteria:

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Nathalie TABIBZADEH, MD Principal Investigator Assistance Publique - Hôpitaux de Paris
Overall Contact

Last name: Nathalie TABIBZADEH, MD

Phone: + 33 1 56 01 83 29

Email: [email protected]

Location
facility contact contact_backup
Department : Exploration fonctionnelles rénales, Centre de la lithiase Hôpital TENON Nathalie TABIBZADEH, MD + 33 1 56 01 83 29 [email protected]
Location Countries

France

Verification Date

July 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Potassium and magnesium citrate

Arm group type: Experimental

Description: Patients are treated with potassium and magnesium citrate

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: Patients are treated with placebo

Acronym CiRUS
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov