Randomized controlled trial to compare the efficacy and safety of oral paricalcitol with oral calcitriol in dialysis patients with secondary hyperparathyroidism.

AIM: The objective of the study was to compare the efficacy and safety of oral paricalcitol with oral calcitriol for treating secondary hyperparathyroidism. METHODS: We conducted the first multicenter open-labelled parallel group randomized controlled trial in 66 patients on dialysis. Patients were randomized to paricalcitol or calcitriol at a 3:1 dose ratio and adjusted to maintain intact parathyroid hormone (iPTH) level between 150-300 pg/mL, serum calcium ≤2.74 mmol/L and calcium-phosphate product ≤5.63 mmol(2) /L(2). The primary end point was the proportion of patients who achieved >30% reduction in iPTH. RESULTS: At 24 weeks, 22 (61.1%) patients in the paricalcitol and 22 (73.3%) in the calcitriol group had achieved the primary end-point (P-value = 0.29). The cumulative proportion of patients who achieved the end-point at 6 weeks, 12 weeks and 24 weeks were 50%, 80.6% and 86.1%, respectively, in paricalcitol and 53.3%, 86.7% and 86.7%, respectively, in the calcitriol group (P-value = 0.67). Median time to the end-point was 6 weeks in both groups. There were no significant differences in iPTH level at any time during the study. The median reduction in iPTH at 24 weeks was 48.4% in the paricalcitol group and 41.9% in the calcitriol group (P-value = 0.6). The median maximal iPTH reduction was 77.1% (paricalcitol) and 83.7% (calcitriol), P-value = 0.3. Serum calcium and incidence of hypercalcaemia did not differ between groups. 16.7% of patients in both groups had at least one episode of hypercalcaemia (serum calcium >2.74 mmol/L). Other adverse events were similar between groups. CONCLUSION: Our study suggests that oral paricalcitol has similar efficacy and safety to oral calcitriol.

A randomized, multicenter, open-label trial to determine peritonitis rate, product defect, and technique survival between ANDY-Disc and UltraBag in patients on CAPD.

BACKGROUND: With the various twin-bag systems available on the market, we decided to conduct a therapeutic equivalence study comparing ANDY-Disc (Fresenius Medical Care, Bad Homburg, Germany) with UltraBag (Baxter, Deerfield, IL) in patients on continuous ambulatory peritoneal dialysis (CAPD) therapy. METHODS: This multicenter, open-label, parallel-group, randomized trial is designed to show the therapeutic equivalence of ANDY-Disc with UltraBag. All CAPD patients from the 6 participating centers who met inclusion/exclusion criteria were enrolled into the trial. They were randomly assigned and converted from the Y-disconnect system (Ultraset; Baxter) to the twin-bag systems. The primary outcome variable is peritonitis, and secondary outcome parameters are technique failure or product defect. RESULTS: From April 2002 to May 2003, a total of 270 patients were recruited for this study. Overall peritonitis rates were 22.9 patient-months/episode for ANDY-Disc and 35.0 patient-months/episode for UltraBag. The overall peritonitis rate for ANDY-Disc was 53% greater compared with UltraBag, but the 95% confidence interval overlaps the prespecified margin of equivalence. There were more product defects reported with ANDY-Disc; 236 product defects compared with 17 with UltraBag. The time series of the number of product defects and peritonitis count on the ANDY-Disc arm suggests a possible cause-and-effect relationship. CONCLUSION: Therapeutic equivalence of ANDY-Disc to UltraBag could not be established with respect to peritonitis. There is a trend toward greater risk for peritonitis on the Andy-Disc arm. There also is a suggestive cause-and-effect relation between the occurrence of product defect and peritonitis on the ANDY-Disc arm during the early part of the trial.

Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.

BACKGROUND: The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. METHODS: Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75-1 g/m(2) monthly for 6 months in addition to corticosteroids. RESULTS: Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side-effects. CONCLUSIONS: MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.

A randomized, multicenter, open-label trial to establish therapeutic equivalence between the Carex and ultra disconnect systems in patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: In the present study, we undertook to establish therapeutic equivalence with respect to peritonitis and technique failure between the Carex disconnect system (B. Braun Carex, Mirandola, Italy) and the standard Ultra system (Baxter Healthcare, Tokyo, Japan) in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This multicenter, parallel group, randomized controlled trial involved 363 prevalent CAPD patients from 8 centers. The primary endpoint was peritonitis rate; secondary endpoints were technique failure and technical problems encountered. The duration of the evaluation was 1 year. RESULTS: The risk of peritonitis on Carex varied between the centers. We found a significant treatment-center interaction effect (likelihood ratio test: p = 0.03). The incidence rate ratio (IRR) of peritonitis on Carex as compared with Ultra ranged from 0.4 to 7.2. In two centers, Carex was inferior to Ultra with regard to peritonitis; but, in five centers, the results were inconclusive. Equivalence was not demonstrated in any center. The overall rate of peritonitis in the Carex group was twice that in the Ultra group [IRR: 2.18; 95% confidence interval (CI): 1.51 to 3.14]. Technique failure and technical problems were more common with the Carex system. Technique failure rate at 1 year was 44% in the Carex group and 22% in the Ultra group. CONCLUSIONS: Equivalence between the Carex disconnect system and the Ultra disconnect system could not be demonstrated. The risk of peritonitis on Carex varied significantly between centers.

Health issues in dialysis-dependent female patients.

BACKGROUND: Reproductive health issues in women with end-stage renal disease (ESRD) are often neglected. Data on these issues are also limited. PURPOSE: We set out to describe the reproductive health issues in women being treated with either hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: All adult female patients on chronic dialysis in Hospital Seremban from January 1991 to December 2001 were included in our study. Patients (or their spouses or children) were interviewed regarding the menstrual status of the patient, gynecologic screening tests administered to the patient, and the patient's use of hormone replacement therapy (HRT). RESULTS: We recruited 137 women into the study. Of those women, 52.6% were on HD; the rest were on CAPD. Mean age at diagnosis of ESRD was 46.5 +/- 14.1 years (range: 14 - 82 years), and mean duration on dialysis was 33.3 months (range: 2 months - 18 years). Responses about menstrual status were obtained for 118 patients. Of those 118 patients, 55 (46.6%) were postmenopausal at dialysis initiation. Average age at menopause had been 48.5 +/- 4.9 years. Another 19 patients (16.1%) had still been menstruating at dialysis initiation, but subsequently entered menopause. Their average age at menopause had been 45.1 +/- 10.3 years. The remaining 44 patients (37.3%) were still menstruating at an average age of 35.7 years (range: 15 - 49 years). Only 3 of 73 responders were on HRT; 63% had undergone a Pap smear; and 54% had had a breast examination. CONCLUSIONS: Patients with ESRD tend to experience premature menopause. Not all dialysis patients are amenorrheic. Despite frequent contact between dialysis patients and hospital staff, gynecologic screening and use of HRT in those patients are still very low.