SimSepT: Simvastatin and severe sepsis in the ICU - SimSepT

Phase 1

• Conditions: Severe sepsis

• Registration Number: EUCTR2005-003438-17-GB
• Lead Sponsor: Oxford Radcliffe Hospitals NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2005-10-04
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Patients eligible for inclusion will be those admitted to an Adult Intensive Care Unit, with a known or suspected infection on the basis of clinical data at the time of screening and signs of severe sepsis (appendix 1a and 1b) or those who develop severe sepsis whilst in intensive care. Patients must be randomised within 24-hours of first recorded organ dysfunction to be included in the study. The first dose of SimSept trial drug (placebo or simvastatin) must be given within 24-hours of randomisation.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients will be excluded from the trial if they:
•are receiving simvastatin or another statin prior to admission,
•refuse consent or their relatives refuse assent,
•are less than 16-years of age,
•are included in another interventional study,
•have a known adverse reaction to statins,
•have an indication or contraindication to treatment with a statin, according to the treating physician,
•are unable to receive enteral medications,
•are receiving drugs known to interact with simvastatin,
•have active liver disease,
•have severe renal impairment (anuria, creatinine >400µmol.l-1or requirement for renal replacement therapy despite adequate haemodynamic resuscitation),
•are at high risk of rhabdomyolysis (multiple trauma, crush injuries, extensive burns, baseline creatinine kinase (CK) = five-times upper limit of normal (ULN)),
•have a history of known or suspected porphyria,
•are unlikely to survive more than 24h,
•are unable to speak English (or whose relatives are unable to speak English) and a suitable interpreter cannot be found.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: This study will be the first double-blind, randomised, controlled trial of simvastatin versus placebo in the treatment of severe sepsis in humans. It will investigate the effect of simvastatin on important inflammatory markers and monitor the safety and feasibility of administering simvastatin to patients with severe sepsis. If simvastatin has a significant effect on the inflammatory cascade in vivo there will be a sound biological rationale for proceeding with a large, multi-centre trial of simvastatin in severe sepsis.;Secondary Objective: Does administration of 40mg simvastatin to patients with severe sepsis reduce: <br>a) plasma concentration of other markers of sepsis (CRP, procalcitonin) compared with patients receiving placebo,<br>b) hospital mortality compared with patients receiving placebo,<br>c) resource usage in survivors (hospital length of stay) compared with patients receiving placebo.<br>;Primary end point(s): Completion of a 7 day course of trial drug (placebo/simvastatin)