UrolithiasisPhase 3CiRUSNCT04021381
Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi
A Phase 3 study testing Potassium and magnesium citrate in people with Urolithiasis and Calyx; Calculus, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urolithiasis, Calyx; Calculus
- What is being tested?
- Potassium and magnesium citrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 262 participants
- Where
- 1 siteFrance
- Study dates
- 25 Sep 2020to Jun 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Department : Exploration fonctionnelles rénales, Centre de la lithiase Hôpital TENON
Paris, 75020
Nathalie TABIBZADEH, MD, + 33 1 56 01 83 29, nathalie.tabibzadeh@aphp.fr
Jean-Philippe HAYMANN, PU-PH, + 33 1 56 01 67 74, jean-philippe.haymann@aphp.fr
About this study
Official title: Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi: a Randomized Placebo Controlled Trial
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.
Read more
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).
Read the 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.
- Conditions
- Urolithiasis, Calyx; Calculus
- Being tested
- Potassium and magnesium citrate, Placebo
- Keywords
- Urolithiasis, Urinary Calculi, Ureteroscopy, Residual fragments, Morphoconstitutional analysis, Citrate
- Medical subject headings
- Urolithiasis, Calculi, Urinary Calculi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium and magnesium citrateDietary supplement
Also called Lithos
Patients are treated with potassium and magnesium citrate 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis.
PlaceboDietary supplement
Patient are treated with placebo 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis.
| Study group | Role | What they receive |
|---|---|---|
| Potassium and magnesium citrate | Experimental | Patients are treated with potassium and magnesium citrate Receives: Dietary Supplement: Potassium and magnesium citrate |
| Placebo | Placebo comparator | Patients are treated with placebo Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stone-free result
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.
Measured: 3 months
Secondary outcomes (5)
SFR score 2, 3 and 4
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
Measured: 3 months
Urine supersaturation index
Urine supersaturation index calculation based on the combination of urine pH, calciuria, phosphaturia, uricosuria, oxaluria) at 3 months in the two groups
Measured: 3 months
To evaluate the Safety of potassium and magnesium citrate: Percentage of patients with at least one adverse event throughout the study
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.
Measured: 3 months
To evaluate the compliance of potassium and magnesium citrate as assessed by citraturia
24-hour and fasting citraturia (mmol/L) at 3 months.
Measured: 3 months
To evaluate the compliance of potassium and magnesium citrate as assessed by urinary pH
24-hour and fasting pH at 3 months.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start25 Sep 2020
- Primary completionMar 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for UrolithiasisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 262 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nathalie TABIBZADEH, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021381
- Sponsor's protocol ID
- P170933J
- Other IDs
- 2018-A03500-55
- Acronym
- CiRUS
- Status last verified
- Oct 2021
- First submitted
- 24 May 2019
- Last updated
- 20 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Citrate Salts for Stone-free Result After Flexible Ureterorenoscopy for Inferior Calyx Calculi: a Randomized Placebo Controlled Trial
- ClinicalTrials.gov ID
- NCT04021381
- Acronym / sponsor ID
- CiRUS / P170933J
- Conditions
- Urolithiasis, Calyx; Calculus
- Keywords
- Urolithiasis, Urinary Calculi, Ureteroscopy, Residual fragments, Morphoconstitutional analysis, Citrate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 262 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 25 Sep 2020 (actual)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 16 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Potassium and magnesium citrate | Experimental | Dietary Supplement: Potassium and magnesium citratePatients are treated with potassium and magnesium citrate |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPatients are treated with placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Potassium and magnesium citrateAlso: LithosPatients are treated with potassium and magnesium citrate 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis. | Dietary supplement | Potassium and magnesium citrate |
| PlaceboPatient are treated with placebo 5.2 grams daily during 3 months, following flexible ureterorenoscopy for inferior calyx urolithiasis. | Dietary supplement | Placebo |
Primary outcome
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.
5 secondary outcomes
SFR score 2, 3 and 4
Time frame: 3 months
Urine supersaturation index
Time frame: 3 months
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
To evaluate the compliance of potassium and magnesium citrate as assessed by citraturia
Time frame: 3 months
To evaluate the compliance of potassium and magnesium citrate as assessed by urinary pH
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathalie TABIBZADEH, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Potassium and magnesium citrate in people with Urolithiasis and Calyx; Calculus, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nathalie TABIBZADEH, MD (+ 33 1 56 01 83 29, nathalie.tabibzadeh@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stone-free result (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2021.