The efficacy and safety of citrate mixture vs sodium bicarbonate on urine alkalization in Chinese primary gout patients with benzbromarone: a prospective, randomized controlled study

Abstract

Objectives To compare the efficacy and safety of citrate mixture and sodium bicarbonate on urine alkalization in gout patients under benzbromarone treatment. Methods A prospective, randomized, parallel controlled trial was conducted among 200 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. The participants were randomly divided into two groups (1:1), sodium bicarbonate group (3 g/day) and citrate mixture group (7 g/day). All patients were prescribed with 25 mg/day benzbromarone at initiation and maintained at a dose of 50 mg/day. Clinical and biochemical data were collected at each follow-up time point (baseline, weeks 2, 4, 8 and 12). Results A total of 182 patients completed the 12-week urine alkalization study. The urine pH value of both groups increased significantly from the baseline to the final follow-up time point (sodium bicarbonate group, 5.50–6.00, P < 0.05; citrate mixture group, 5.53–5.93, P < 0.05). While the comparisons regarding urine pH between treatment groups showed no significant differences for each time point. The estimated glomerular filtration rate (eGFR) dropped significantly after 12 weeks’ trial in the sodium bicarbonate group (P < 0.01), while it was comparable between baseline and the last follow-up (P > 0.05) in the citrate mixture group. Results of urine analysis showed that the incident rate of occult blood in the sodium bicarbonate group was higher than that in the citrate mixture group (38 vs 24%, P < 0.05), accompanied by a similar occurrence of kidney stones. After 12-week follow-up, the frequency of twice gout flare in the citrate mixture group was significantly lower than that in sodium bicarbonate group (4 vs 12%, P = 0.037). No treatment-emergent adverse events occurred. Conclusion The efficacy of citrate mixture on urine alkalization is comparable to sodium bicarbonate under benzbromarone treatment without significant adverse events. Citrate mixture is superior to sodium bicarbonate in lowering the incidence of urine occult blood and the frequency of gout attacks. Trial registration Registered with ChiCTR (http://www.chictr.org.cn), No. ChiCTR1800018518.

Superiority of Low‐Dose Benzbromarone to Low‐Dose Febuxostat in a Prospective, Randomized Comparative Effectiveness Trial in Gout Patients With Renal Uric Acid Underexcretion

“…In this study, the incidence of urolithiasis in the LDBen group (5%) was numerically but not significantly higher than that in the LDFeb group (2%). Incidence rates of urolithiasis of ~3% have been reported with benzbromarone 75-120 mg/day (37,38), including in a trial in China using benzbromarone 25 mg/day (16), similar to our results.…”

“…Treatment and procedures. As described in the previous study (16), all participants enrolled in the trial underwent a 14-day washout period, which indicated that they stopped receiving urate-lowering drugs and adhered to a low-purine diet. During the study, other urate-lowering drugs or drugs that are known to affect the serum urate level were prohibited.…”

Effect of Alkalized Urine on Renal Calculi in Patients With Gout: a Protocol for a Randomized Controlled Trial

“…(6) Other investigators consider that the subject is not suitable to continue and need to quit; (7) Compliance of the subject to the research protocol is poor, and the quantity and duration of medication are not between 80% and 120%.…”

“…Another study suggested that the pH value of urine is increased from 5.5-6.0 by administering sodium bicarbonate (1 g tid) for 3 months in patients with gout [7] . Although several Associations of Urology recommended urine alkalization to promote calculi dissolution in nephrolithiasis [8][9][10][11] , advanced evidence is lacking.…”

Effect of alkalized urine on renal calculi in patients with gout: a protocol for a placebo-controlled, double-blinded randomized controlled trial

“…Another study suggested that the pH value of urine increased from 5.5 to 6.0 by administering sodium bicarbonate (1 g tid) for 3 months in gout patients [ 7 ]. Although several urological associations recommended urine alkalization to promote calculi dissolution in nephrolithiasis [ 8 – 11 ], advanced evidence is lacking.…”