Dataset Information

Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial.

ABSTRACT:

Background

There is no treatment for septic acute kidney injury (sAKI). The anti-inflammatory activity of prolonged-release pirfenidone (PR-PFD) could be beneficial in this clinical setting.

Methods

This study was a double-blind randomized clinical trial in sAKI patients with nephrology consultation at the Civil Hospital of Guadalajara, in addition to the usual treatment of AKI associated with sepsis; patients were randomized to receive either PR-PFD at 1,200?mg/day (group A) or 600?mg/day (group B) or a matched placebo for 7 consecutive days. The primary objective was the decrease in serum creatinine (sCr) and increase in urinary volume (UV); the secondary objectives were changes in serum electrolytes, acid-base status, and mortality.

Results

Between August 2016 and August 2017, 88 patients were randomized. The mean age was 54 (17?±?SD) years, and 47% were male. The main site of infection was the lung (39.8%), septic shock was present in 39.1% of the cases, and the mean SOFA score was 8.8 points. 28 patients received PFD 1,200?mg, 30 patients received PFD 600?mg, and 30 patients received placebo. During the study, sCr did not differ among the groups. The reversion rate of sCr, UV, and mortality was not different among the groups (p=0.70, p=0.47, and p=0.38, respectively). Mild adverse events were not different among the groups.

Conclusion

PR-PFD did not improve the clinical course of sAKI and seemed to be safe in terms of adverse events. This trial is registered with NCT02530359.

SUBMITTER: Chavez-Iniguez JS

PROVIDER: S-EPMC7817311 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial.

Chávez-Iñiguez Jonathan S JS Poo Jorge L JL Ibarra-Estrada Miguel M García-Benavides Leonel L Navarro-Blackaller Guillermo G Cervantes-Sánchez Cynthia C Nungaray-Pacheco Eduardo E Medina-González Ramón R Armendariz-Borunda Juan J García-García Guillermo G

International journal of nephrology 20210113

<h4>Background</h4>There is no treatment for septic acute kidney injury (sAKI). The anti-inflammatory activity of prolonged-release pirfenidone (PR-PFD) could be beneficial in this clinical setting.<h4>Methods</h4>This study was a double-blind randomized clinical trial in sAKI patients with nephrology consultation at the Civil Hospital of Guadalajara, in addition to the usual treatment of AKI associated with sepsis; patients were randomized to receive either PR-PFD at 1,200 mg/day (group A) or 6 ...[more]

PMID: 33520317

Similar Datasets

Project description:IntroductionTo evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed.MethodsThirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.ResultsThere was a significant (P=0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50±27 to 108±73 mL/minute (mean±SEM) for the AP group; and from 40±37 to 65±30 mL/minute for placebo; P=0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.ConclusionsThe improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.Trial registrationwww.clinicaltrials.gov: NCT00511186.

Project description:BackgroundAcute kidney injury (AKI) is a common and serious complication after cardiac surgery, and current strategies aimed at treating AKI have proven ineffective. Levosimendan, an inodilatating agent, has been shown to increase renal blood flow and glomerular filtration rate in uncomplicated postoperative patients and in patients with the cardiorenal syndrome. We hypothesized that levosimendan through its specific effects on renal vasculature, a preferential vasodilating effect on preglomerular resistance vessels, could improve renal function in AKI-patients with who did not have clinical indication for inotropic support.MethodsIn this single-center, double-blind, randomized controlled study, adult patients with postoperative AKI within 2 days after cardiac surgery, who were hemodynamically stable with a central venous oxygen saturation (ScvO2) ≥ 60% without inotropic support were eligible for inclusion. After randomization, study drug infusions, levosimendan (n = 16) or placebo (n = 13) were given for 5 h. A bolus infusion of levosimendan (12 µg/kg), were given for 30 min followed by 0.1 µg/kg/min for 5 h. Renal blood flow and glomerular filtration rate were measured using infusion clearance of para-aminohippuric acid and a filtration marker, respectively. As a safety issue, norepinephrine was administered to maintain mean arterial pressure between 70-80 mmHg. Intra-group differences were tested by Mann-Whitney U-tests, and a linear mixed model was used to test time and group interaction.ResultsTwenty-nine patients completed the study. At inclusion, the mean serum creatinine was higher in the patients randomized to levosimendan (148 ± 29 vs 127 ± 22 µmol/L, p = 0.030), and the estimated GFR was lower (46 ± 12 vs 57 ± 11 ml/min/1.73 m2, p = 0.025). Levosimendan induced a significantly (p = 0.011) more pronounced increase in renal blood flow (15%) compared placebo (3%) and a more pronounced decrease in renal vascular resistance (- 18% vs. - 4%, respectively, p = 0.043). There was a trend for a minor increase in glomerular filtration rate with levosimendan (4.5%, p = 0.079), which did differ significantly from the placebo group (p = 0.440). The mean norepinephrine dose was increased by 82% in the levosimedan group and decreased by 29% in the placebo group (p = 0.012).ConclusionsIn hemodynamically stable patients with AKI after cardiac surgery, levosimendan increases renal blood flow through renal vasodilatation. Trial registration NCT02531724, prospectly registered on 08/20/2015. https://clinicaltrials.gov/ct2/show/NCT02531724?cond=AKI&cntry=SE&age=1&draw=2&rank=1.

Project description:INTRODUCTION:Melatonin, secreted by the pineal gland during the night phase, is a regulator of the biological clock and sleep tendency. Totally blind subjects frequently report severe, periodic sleep problems, with 50%-75% of cases displaying non-24-hour sleep-wake disorder (N24HSWD) due to inability to synchronize with the environmental day-night cycle. Melatonin immediate-release preparations are reportedly effective in N24HSWD. Here, we studied the efficacy and safety of prolonged-release melatonin (PRM), a registered drug for insomnia, for sleep disorders in totally blind subjects living in normal social environments. The primary endpoint was demonstration of clinically meaningful effects on sleep duration (upper confidence interval [CI] limit >20 minutes whether significant or not) to allow early decision-making on further drug development in this indication. TRIAL REGISTRATION:ClinicalTrials.gov registry - NCT00972075. METHODS:In a randomized, double-blind, placebo-controlled proof-of-principle study, 13 totally blind subjects had 2 weeks' placebo run-in, 6 weeks' randomized (1:1) PRM (Circadin(®)) or placebo nightly, and 2 weeks' placebo run-out. Outcome measures included daily voice recorded sleep diary, Clinical Global Impression of Change (CGIC), WHO-Five Well-being Index (WHO-5), and safety. RESULTS:Mean nightly sleep duration improved by 43 minutes in the PRM and 16 minutes in the placebo group (mean difference: 27 minutes, 95% CI: -14.4 to 69 minutes; P=0.18; effect size: 0.82) meeting the primary endpoint. Mean sleep latency decreased by 29 minutes with PRM over placebo (P=0.13; effect size: 0.92) and nap duration decreased in the PRM but not placebo group. The variability in sleep onset/offset and latency tended to decrease during PRM but not placebo treatment. The potentially beneficial effects of PRM persisted during the 2 weeks of discontinuation period, consistent with clock stabilizing effects. PRM was well-tolerated, adverse events were of mild or moderate severity and similar between PRM and placebo. CONCLUSION:Nightly use of PRM may potentially improve patient-reported sleep difficulties in totally blind individuals trying to adhere to normal social lifestyle. A larger study powered to demonstrate a statistically significant effect is warranted.

Dataset Information

Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial.

Background

Methods

Results

Conclusion

Publications

Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets