Clinical trial NCT03346369: Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis
Official title: Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis: a Short-term, Prospective, Open-label, Efficacy and Safety Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Secondary Hyperoxaluria
Nephrolithiasis
Keywords: Nephrolithiasis
Urolithiasis
Secondary Hyperoxaluria
Hyperoxaluria
Lanthanum Carbonate
Phosphate Binder
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2017-11-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study investigates the efficacy and the safety of Lanthanum Carbonate for the reduction of urinary oxalate excretion in patients with secondary hyperoxaluria and nephrolithiasis. Patients will be treated during 2 consecutive 14-day treatment periods with a low and a high dose of Lanthanum Carbonate respectively.
Primary purpose: TREATMENT

Brief summary: This study investigates the efficacy and the safety of Lanthanum Carbonate for the reduction of urinary oxalate excretion in patients with secondary hyperoxaluria and nephrolithiasis.

Detailed description: Nephrolithiasis/urolithiasis is a prevalent (overall lifetime risk up to 13% in Western countries) and highly recurrent disease. Secondary hyperoxaluria is a key risk factor for the development of calcium oxalate stones, the most frequent stone type. Currently used therapeutic options in secondary hyperoxaluria have limited efficacy. Recent findings in vitro and in a rat model, provided evidence that Lanthanum Carbonate is an effective oxalate binder. The objective of this study is to investigate whether treatment with Lanthanum Carbonate reduces urinary oxalate excretion in human subjects with secondary hyperoxaluria and nephrolithiasis. By treating the patients with two different doses of Lanthanum Carbonate during two 14-day treatment periods, a dose-response will be evaluated.

Eligibility criteria: Inclusion Criteria:

* able to give written informed consenct
* hyperoxaluria (defined as urinary oxalate \> 45 mg/24 hours), demonstrated on 24-hour urine collection within 18 months prior to baseline visit
* history of nephrolithiasis eGFR \> 60 mL/min/1.73m² (CKD-EPI formula)

Exclusion Criteria:

* primary hyperoxaluria, diagnosed by genetic testing
* known allergy to Lanthanum Carbonate
* hypophosphatemia (defined as serum phosphorus \< 0.81 mmol/L)
* severe known liver insufficiency of biliary obstruction
* rectocolitis ulcerohaemorraghica, Crohn's disease, bowel obstruction, stomach/duodenal ulceration
* glucose/galactose malabsorption
* severe diarrhea or other gastrointestinal disorder, which might interfere with the ability to absorb oral medication
* pregnancy or breast-feeding
* female participant of childbearing potential unwilling to take efficient contraceptive measures for the duration of the study
* female participant without negative serum or urine pregnancy test
* psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study
* currently participating in another clinical trial

Primary outcomes:
measure: The mean reduction in urinary oxalate excretion in patients treated with a daily Lanthanum Carbonate dose of 750 mg
timeFrame: After the first 14-day treatment period
Secondary outcomes:
measure: The incremental reduction in mean urinary oxalate excretion after doubling the dose of Lanthanum Carbonate from 750 mg tot 1500 mg daily
timeFrame: After the second 14-day treatment period
measure: The proportion of patients developing severe hypophosphatemia
timeFrame: After the first and second 14-day treatment period
measure: The evolution of phosphaturia, evaluated by 24-hour urinary phosphorus excretion
timeFrame: After the first and second 14-day treatment period
measure: The evolution of phosphaturia, evaluated by urinary phosphorus to creatinine ratio
timeFrame: After the first and second 14-day treatment period
measure: The evolution of phosphaturia, evaluated by fractional excretion of phosphorus
timeFrame: After the first and second 14-day treatment period
measure: The proportion of patients developing hypophosphaturia
timeFrame: After the first and second 14-day treatment period
measure: The evolution of calciuria, evaluated by 24-hour urinary calcium excretion
timeFrame: After the first and second 14-day treatment period
measure: The evolution of calciuria, evaluated by urinary calcium to creatinine ratio
timeFrame: After the first and second 14-day treatment period
measure: The evolution of calciuria, evaluated by fractional excretion of calcium
timeFrame: After the first and second 14-day treatment period
measure: The evolution of serum Lanthanum levels
timeFrame: After the first and second 14-day treatment period
measure: Adverse events
timeFrame: After the first and second 14-day treatment period
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: University Hospital Brussels
Study officials:
affiliation: Department of Nephrology, University Hospital Brussels
name: Christian Tielemans, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: