Dataset Information

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial.

ABSTRACT:

Objectives

It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines.

Setting

A tertiary teaching hospital in Barcelona, Spain.

Participants

Thirty-four patients were randomly assigned and included in an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo group).

Intervention

Patients were randomly assigned to receive 20?mg of simvastatin or placebo administered in the first 24?h of hospital admission and once daily thereafter for 4?days.

Outcome

Primary end point was the time from hospital admission to clinical stability. The secondary end points were serum concentrations of inflammatory cytokines and partial pressure of arterial oxygen/fractional inspired oxygen (PaO2/FiO2) at 48?h after treatment administration.

Results

The trial was stopped because enrolment was much slower than originally anticipated. The baseline characteristics of the patients and cytokine concentrations at the time of enrolment were similar in the two groups. No significant differences in the time from hospital admission to clinical stability were found between study groups (median 3?days, IQR 2-5 vs 3?days, IQR 2-5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive protein (p=0.23), tumour necrosis factor-? (p=0.58), interleukin 6 (IL-6; p=0.64), and IL-10 (p=0.61) levels at 48?h of hospitalisation were found between simvastatin and placebo groups. Similarly, transaminase and total creatine kinase levels were similar between study groups at 48?h of hospitalisation (p=0.19, 0.08 and 0.53, respectively).

Conclusions

Our results suggest that the use of simvastatin, 20?mg once daily for 4?days, since hospital admission did not reduce the time to clinical stability and the levels of inflammatory cytokines in hospitalised patients with CAP.

Trial registration number

ISRCTN91327214.

SUBMITTER: Viasus D

PROVIDER: S-EPMC4289727 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial.

Viasus Diego D Garcia-Vidal Carolina C Simonetti Antonella F AF Dorca Jordi J Llopis Ferran F Mestre Mariona M Morandeira-Rego Francisco F Carratalà Jordi J

BMJ open 20150106 1

<h4>Objectives</h4>It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines.<h4>Setting</h4>A tertiary teaching hospital in Barcelona, Spain.<h4>Parti ...[more]

PMID: 25564143

Similar Datasets

Project description:IntroductionSulforaphane can induce the transcription factor, Nrf2, promoting antioxidant and anti-inflammatory responses. In this study, hospitalised patients with community-acquired pneumonia (CAP) were treated with stabilised synthetic sulforaphane (SFX-01) to evaluate impact on clinical status and inflammation.MethodsDouble-blind, randomised, placebo-controlled trial of SFX-01 (300 mg oral capsule, once daily for 14 days) conducted in Dundee, UK, between November 2020 and May 2021. Patients had radiologically confirmed CAP and CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) score ≥1. The primary outcome was the seven-point World Health Organization clinical status scale at day 15. Secondary outcomes included time to clinical improvement, length of stay and mortality. Effects on Nrf2 activity and inflammation were evaluated on days 1, 8 and 15 by measurement of 45 serum cytokines and mRNA sequencing of peripheral blood leukocytes.ResultsThe trial was terminated prematurely due to futility with 133 patients enrolled. 65 patients were randomised to SFX-01 treatment and 68 patients to placebo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the cause of CAP in 103 (77%) cases. SFX-01 treatment did not improve clinical status at day 15 (adjusted OR 0.87, 95% CI 0.41-1.83; p=0.71), time to clinical improvement (adjusted hazard ratio (aHR) 1.02, 95% CI 0.70-1.49), length of stay (aHR 0.84, 95% CI 0.56-1.26) or 28-day mortality (aHR 1.45, 95% CI 0.67-3.16). The expression of Nrf2 targets and pro-inflammatory genes, including interleukin (IL)-6, IL-1β and tumour necrosis factor-α, was not significantly changed by SFX-01 treatment. At days 8 and 15, respectively, 310 and 42 significant differentially expressed genes were identified between groups (false discovery rate adjusted p<0.05, log2FC >1).ConclusionSFX-01 treatment did not improve clinical status or modulate key Nrf2 targets in patients with CAP primarily due to SARS-CoV-2 infection.

Project description:BackgroundSeveral trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia).MethodsThis predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence.ResultsFrom the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension.ConclusionsIn patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP.Trial registrationThis trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.

Project description:Background:To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400?mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI). Methods:A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18-70?years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7?days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (? 102 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014-001321-32. Findings:180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P?=?.894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P?=?.601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P?=?.895). Interpretations:A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI. Primary funding source:The Danish Regions [no. 14/217].

Project description:IntroductionParkinson's disease (PD) is a progressive neurodegenerative condition affecting approximately 185,000 people in the UK. No drug has been proven to slow disease progression. Epidemiological and pre-clinical data support simvastatin, a widely used cholesterol-lowering drug with a well-established safety profile, having neuroprotective properties. The aim of this study (Simvastatin as a neuroprotective treatment for PD (PD STAT)) is to determine whether simvastatin has the potential to slow PD progression. The study is part of the International Linked Clinical Trials initiative coordinated by The Cure Parkinson's Trust. This paper describes the protocol for the PD STAT study.Methods and analysisPD STAT is a double-blind, randomised, placebo-controlled, multi-centre, parallel group, futility trial in patients with PD of mild-moderate severity. 235 participants have been recruited and randomly allocated in a 1:1 ratio to receive either oral simvastatin or matched placebo. Treatment involves a 1-month low-dose phase (40 mg daily), followed by a 23-month high-dose phase (80 mg daily) and ends with a 2-month washout period. Participants are reviewed at clinic visits at 1 month, 6, 12, 18, 24 and 26 months post-baseline, with interim telephone follow-up to monitor for adverse events.The primary outcome is the change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III motor subscale score in the practically defined OFF medication state (OFF state) between baseline and 24 months. Primary analysis will be on a modified intention to treat basis and will include only those participants who progress to the high-dose phase of the study.Ethics and disseminationThe protocol has been approved by the North East-Newcastle and North Tyneside 2 Research Ethics Committee. The results will be disseminated via research articles in peer-reviewed journals and presentations at local, national and international scientific meetings, as well as disseminated via patient groups, websites and networks. A summary of the study findings will be posted to participants at the end of the study.Trial registrationISRCTN16108482 (prospectively registered); EudraCT 2015-000148-40; ClinicalTrials.gov NCT02787590; Pre-results.

Dataset Information

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial.

Objectives

Setting

Participants

Intervention

Outcome

Results

Conclusions

Trial registration number

Publications

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets