E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
Does administration of 40mg simvastatin to patients with severe sepsis reduce: a) plasma concentration of other markers of sepsis (CRP, procalcitonin) compared with patients receiving placebo, b) hospital mortality compared with patients receiving placebo, c) resource usage in survivors (hospital length of stay) compared with patients receiving placebo.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Completion of a 7 day course of trial drug (placebo/simvastatin) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will cease when the study has 104 complete data sets. The trial will only be stopped prematurely if mandated to by the Ethics committee or competent authority or following recommendations from the interim data monitoring. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |