Dataset Information

Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification.

ABSTRACT:

Background

The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants.

Methods

Adult patients on maintenance haemodialysis (?6?months) with an Agatston coronary artery calcium score, as measured by a multidetector computed tomography scanner, of 100-3500 U were enrolled. Patients were stratified by Agatston score (100-<400, 400-1000 or >1000 U) and randomized in a 1:1:1 ratio to receive placebo, SNF472 300?mg or SNF472 600?mg administered intravenously three times weekly during each haemodialysis session.

Results

Overall, 274 patients were randomized. The mean age of trial participants was 63.6?(standard deviation 8.9) years and 39% were women. The coronary artery, aorta and aortic valve median (25th-75th percentile) Agatston scores at baseline were 730 U (315-1435), 1728 U (625-4978) and 103 U (31-262), respectively, and the median (25th-75th percentile) calcium volume scores at baseline were 666 (310-1234), 1418 (536-4052) and 107 (38-278), respectively. Older age and diabetes mellitus were associated with higher calcium scores at baseline.

Conclusions

The CaLIPSO trial enrolled patients on haemodialysis with pre-existent cardiovascular calcification to test the hypothesis that SNF472 attenuates its progression in the coronary arteries, aorta and aortic valve.

SUBMITTER: Bellasi A

PROVIDER: S-EPMC7857813 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification.

Bellasi Antonio A Raggi Paolo P Bover Jordi J Bushinsky David A DA Chertow Glenn M GM Ketteler Markus M Rodriguez Mariano M Sinha Smeeta S Salcedo Carolina C Garg Rekha R Gold Alex A Perelló Joan J

Clinical kidney journal 20191030 1

<h4>Background</h4>The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants.<h4>Methods</h4>Adult patients on maintenance haemodialysis (≥6 months) with an Agatston coronary artery calcium score, as m ...[more]

PMID: 33564440

Similar Datasets

Project description:BackgroundConstipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients. In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days.ResultsOnly 318 (20.6%) of the 1542 screened adults during the 1/17-10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N (n = 6) and P (n = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P = 1.0). No patient experienced opioid withdrawal.ConclusionsImportant recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research.

Project description:BackgroundVitamin K occurs in the diet as phylloquinone and menaquinones. Observational studies have shown that both phylloquinone and menaquinone intake might reduce cardiovascular disease (CVD) risk. However, the effect of vitamin K on vascular calcification is unknown.ObjectivesThe aim of this study was to assess if menaquinone supplementation, compared to placebo, decreases vascular calcification in people with type 2 diabetes and known CVD.MethodsIn this double-blind, randomized, placebo-controlled trial, we randomly assigned men and women with type 2 diabetes and CVD to 360 µg/d menaquinone-7 (MK-7) or placebo for 6 mo. Femoral arterial calcification at baseline and 6 mo was measured with 18sodium fluoride positron emission tomography (18F-NaF PET) scans as target-to-background ratios (TBRs), a promising technique to detect active calcification. Calcification mass on conventional computed tomography (CT) scan was measured as secondary outcome. Dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were measured to assess compliance. Linear regression analyses were performed with either TBR or CT calcification at follow-up as the dependent variable, and treatment and baseline TBR or CT calcification as independent variables.ResultsWe randomly assigned 35 patients to the MK-7 group (33 completed follow-up) and 33 to the placebo group (27 completed follow-up). After the 6-mo intervention, TBR tended to increase in the MK-7 group compared with placebo (0.25; 95% CI: -0.02, 0.51; P = 0.06), although this was not significant. Log-transformed CT calcification mass did not increase in the intervention group compared with placebo (0.50; 95% CI: -0.23, 1.36; P = 0.18). MK-7 supplementation significantly reduced dp-ucMGP compared with placebo (-205.6 pmol/L; 95% CI: -255.8, -155.3 pmol/L). No adverse events were reported.ConclusionMK-7 supplementation tended to increase active calcification measured with 18F-NaF PET activity compared with placebo, but no effect was found on conventional CT. Additional research investigating the interpretation of 18F-NaF PET activity is necessary. This trial was registered at clinicaltrials.gov as NCT02839044.

Project description:BackgroundRuxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis.MethodsIn this double-blind trial, we randomly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients). The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic resonance imaging. Secondary end points included the durability of response, changes in symptom burden (assessed by the total symptom score), and overall survival.ResultsThe primary end point was reached in 41.9% of patients in the ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A reduction in spleen volume was maintained in patients who received ruxolitinib; 67.0% of the patients with a response had the response for 48 weeks or more. There was an improvement of 50% or more in the total symptom score at 24 weeks in 45.9% of patients who received ruxolitinib as compared with 5.3% of patients who received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence interval, 0.25 to 0.98; P=0.04). The rate of discontinuation of the study drug because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the placebo group. Among patients who received ruxolitinib, anemia and thrombocytopenia were the most common adverse events, but they rarely led to discontinuation of the drug (in one patient for each event). Two patients had transformation to acute myeloid leukemia; both were in the ruxolitinib group.ConclusionsRuxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.).

Dataset Information

Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification.

Background

Methods

Results

Conclusions

Publications

Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets