A randomised Phase I/II trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria.
| Autor: | Hoppe, Bernd, Niaudet, Patrick, Salomon, Rémi, Harambat, Jérôme, Hulton, Sally-Anne, Van't Hoff, William, Moochhala, Shabbir, Deschênes, Georges, Lindner, Elisabeth, Sjögren, Anna, Cochat, Pierre |
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| Předmět: |
FECES
MICROBIOLOGY ANALYSIS of variance CONFIDENCE intervals STATISTICAL correlation GAS chromatography GASTROINTESTINAL system KIDNEY diseases MEDICAL cooperation ORAL drug administration OXALIC acid PATIENT safety PLACEBOS RESEARCH RESEARCH funding STATISTICAL sampling STATISTICS T-test (Statistics) DATA analysis RANDOMIZED controlled trials BLIND experiment ADVERSE health care events DESCRIPTIVE statistics GRAM-negative anaerobic bacteria INBORN errors of carbohydrate metabolism |
| Zdroj: | Pediatric Nephrology; May2017, Vol. 32 Issue 5, p781-790, 10p, 4 Charts, 1 Graph |
| Abstrakt: | Background: Primary hyperoxaluria (PH) is a rare, genetic disorder which involves the overproduction of endogenous oxalate, leading to hyperoxaluria, recurrent urolithiasis and/or progressive nephrocalcinosis and eventually resulting in kidney failure and systemic oxalosis. The aim of this trial was to investigate whether treatment involving an oxalate-metabolising bacterium ( Oxalobacter formigenes) could reduce urinary oxalate excretion in PH patients. Methods: The efficacy and safety of O. formigenes (Oxabact® OC5; OxThera AB, Stockholm, Sweden) was evaluated in a randomised, placebo-controlled, double-blind study for 8 weeks. The primary objective was reduction in urinary oxalate excretion (Uox). Secondary objectives included faecal O. formigenes count and decrease in plasma oxalate concentration (Pox). Results: Twenty-eight patients randomised 1:1 to the treatment group (OC5) or the placebo group completed the study. After 8 weeks of treatment, there was no significant difference in the change in Uox (mmol/24 h/1.73 m) between the groups (OC5: +0.042, placebo: −0.140). Post-hoc analysis showed a statistically significant increase in Uox per urinary creatinine excretion in the OC5 group (OC5: +5.41, placebo: −15.96; p = 0.030). Change in Pox from baseline was not significantly different between groups ( p = 0.438). The O. formigenes cell count was significantly increased in OC5-treated patients ( p < 0.001) versus placebo. The treatment response to O. formigenes was related to individual stage of kidney deterioration, and Pox was directly correlated to kidney function, even for early-stage patients (chronic kidney disease stage 1). No safety issues were observed. Conclusions: Treatment with OC5 did not significantly reduce Uox or Pox over 8 weeks of treatment. The treatment was well tolerated and successfully delivered to the gastrointestinal tract. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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