Randomized,Double‐Blind,Placebo‐Controlled Trial of Spironolactone for Hypokalemia in Continuous Ambulatory Peritoneal Dialysis Patients

The incidence of hypokalemia in continuous ambulatory peritoneal dialysis (CAPD) patients is about 15–60%, leading to significant complications. There is no standard treatment other than potassium supplement in this setting. The aim of this study was to evaluate effect of spironolactone 25 mg/day in CAPD patients who have a history of hypokalemia. This is a randomized, double‐blind, placebo‐controlled, cross‐over study in CAPD patients who had a history of hypokalemia. Study intervention is 4 weeks of oral spironolactone 25 mg/day or placebo, cross‐over after a 2‐week wash‐out period. The primary outcome was the difference of serum potassium before and after 4 weeks of spironolactone treatment. Serum potassium was measured every 2 weeks, serum magnesium, urine and peritoneal fluid potassium measured before and after each treatment period. We enrolled 24 patients, and 20 completed the cross‐over study. Ten patients were anuric. The total doses of potassium supplement were the same during the study period. Serum potassium levels before and after study intervention were not significantly different in both groups (4.23 ± 0.64 vs. 3.90 ± 0.59 mEq/L for spironolactone P = 0.077 and 3.84 ± 0.62 vs. 3.91 ± 0.52 for placebo P = 0.551). Total 24‐h potassium, magnesium, sodium excretion, urine volume and ultrafiltration volume were not affected by spironolactone or placebo. There was one episode of hyperkalemia (5.6 mEq/L) during the spironolactone treatment period. Spironolactone 25 mg/day does not have a significant effect on serum potassium or urine and peritoneal excretion rate in CAPD patients who have a history of hypokalemia.     

Efficacy of Hydroxychloroquine in Hand Osteoarthritis: A Randomized,Double‐Blind,Placebo‐Controlled Trial

Objective

To determine the symptom‐modifying effect of hydroxychloroquine (HCQ) in hand osteoarthritis (OA).

Methods

In this randomized, double‐blind, multicenter trial, patients with symptomatic hand OA received either HCQ 400 mg once a day or placebo during 24 weeks. The primary outcome was change of pain measured on a 100‐mm visual analog scale (VAS) at 24 weeks. Secondary outcomes included decrease of pain at weeks 6 and 12 and change in Australian Canadian Hand Osteoarthritis Index (AUSCAN) and Arthritis Impact Measurement Scale 2 short form (AIMS2‐SF) total scores.

Results

A total of 196 patients was included (placebo n = 98, HCQ n = 98). Mean ± SD age was 58.0 ± 7.6 years, and 86% were female. Baseline mean ± SD pain VAS was 44.9 ± 22.9 mm in the placebo group and 43.2 ± 22.3 mm in the HCQ group. At 24 weeks, change in pain VAS was not significantly different between both groups (imputed mean VAS 42.7 in the HCQ group versus 45.3 in the placebo group after 24 weeks), as was the case in pain VAS at weeks 6 and 12. Changes in AUSCAN total score and AIMS2‐SF total score in both groups were similar between the groups. In total, 24 patients in the placebo group and 21 patients in the HCQ group reported ≥1 adverse event. In the HCQ group, 3 patients reported a severe allergic reaction. Fifteen patients withdrew from the study (5 placebo, 10 HCQ group) due to adverse events.

Conclusion

Treatment with HCQ at 24 weeks is not effective in reducing the symptoms of hand OA compared to placebo.

     

A Double‐Blind,Placebo‐Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol Dependence

Background: This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods: Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12‐week, placebo‐controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions‐Severity of Illness score. Results: Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ?0.36 with quetiapine and ?0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions: The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence.     

A Randomized Double‐Blind Sham‐Controlled Trial of the Prosorba Column for Treatment of Refractory Rheumatoid Arthritis

Abstract: The Prosorba column has been studied as a novel therapy for rheumatoid arthritis in several clinical settings over the last 5 years. In this article, we summarize the pivotal clinical trial study supporting the safety and efficacy of the Prosorba column as it is applied to treatment of rheumatoid arthritis. The Prosorba column is a medical device that contains purified staphylococcal protein A covalently bound to a silica matrix. This device is used to treat patient plasma in conjunction with a plasmapheresis machine. In this ex vivo treatment, blood is withdrawn from the patient, cells are separated from plasma in the machine, and the plasma is passed through the Prosorba column. The plasma then is recombined with the cells and returned to the patient. The Prosorba column was approved for the treatment of idiopathic thrombocytopenic purpura in 1987 and, in 2 open‐label trials 1 , 2 , showed promising evidence of efficacy in rheumatoid arthritis. A subsequent Phase 3 pivotal trial demonstrated statistical superiority of Prosorba treatments to sham column apheresis 3 . Analysis of the pivotal trial of patients who completed all treatments indicated that 41.7% of the Prosorba treated patients met American College of Rheumatology defined response criteria as compared to 15.6% of the sham treated patients. This difference was significant at a level of p ≤ 0.02.