Simvastatin and severe sepsis trial

This trial has now closed.

Inclusion criteria:

  • Admission to an Adult Intensive Care Unit
  • Known or suspected infection on the basis of clinical data at the time of screening
  • Signs of sepsis
  • Within 24 hours of first recorded organ dysfunction

Exclusion criteria:

  • Receiving simvastatin or another statin prior to admission
  • Consent refused or their relatives refuse assent
  • Less than 16-years of age
  • Included in another interventional study
  • Known adverse reaction to statins
  • Known adverse reaction to paracetamol
  • Indication or contraindication to treatment with a statin, according to the treating physician
  • Unable to receive enteral medications
  • Receiving drugs known to interact with simvastatin
  • Active liver disease
  • Severe renal impairment (anuria, creatinine >400μmol.l-1 or requirement for renal replacement therapy despite adequate haemodynamic resuscitation)
  • At high risk of rhabdomyolysis (multiple trauma, crush injuries, extensive burns, baseline creatinine kinase (CK) ≥ five-times upper limit of normal (ULN))
  • History of known or suspected porphyria
  • Unlikely to survive more than 24h
  • Unable to speak English (or whose relatives are unable to speak English) and a suitable interpreter cannot be found.
  • Pregnancy

Simvastatin and severe sepsis trial

ISRCTN 92093279, EudraCT number: 2005-003438-17

Simvastatin is a widely used cholesterol lowering agent which has been shown to reduce mortality from ischaemic heart disease.

More recently it has been found to have widespread anti-inflammatory and immuno-modulatory properties. As a consequence, it has been suggested that simvastatin may have a role in the treatment of sepsis. This argument is supported by data from animal models and case-control studies in humans.

Simvastatin structural formula

This study will be the first double-blind, randomised, controlled trial of simvastatin (40mg) 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.

Patients that are admitted to the Adult Intensive Care Unit at the John Radcliffe Hospital, Oxford and the Adult Intensive Care Units of the Brighton and Sussex University Hospitals NHS Trust and with suspected severe sepsis will be approached to enter the study.

This project has been funded by the Moulton Charitable Trust.
The sponsor of this trial is the Oxford Radcliffe Hospitals NHS Trust.

Trial Coordinator

Dr V S Barber
Kadoorie Centre for Critical Care Research and Education
Level 3
The John Radcliffe Hospital
Headley Way
Headington OXFORD OX3 9DU

Tel: 01865 857626
Fax: 01865 857611
In emergencies: 07900 580999

    Oxford University   Brighton and Sussex University Hospitals NHS Trust

Randomisation service provided by: Sealed Envelope™.com