Sepsis is the clinical syndrome defined by the presence of both infection and a systemic inflammatory response. Sepsis is common in general medical and surgical wards with an estimated prevalence of 15%. The pathophysiological process of sepsis is a disease continuum from infection, signs of systemic inflammation in response to infection, sepsis, severe sepsis and multi-organ dysfunction. Sepsis may convert to severe sepsis resulting in a higher hospital mortality rate.
Conditions
Interventions
Product Name: Atorvastatin
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Heart of England NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A. Age > 18 years; B. One of following documented source of infection: (1). Pneumonia is defined as clinical signs: cough or new sputum production or dyspnoea or chest pain or rales and an infiltrate on CXR; (2). Urinary tract infection is defined as > 1 of following criteria: urgency or frequency, or dysuria, or suprapubic tenderness and > 1 of the following: a. positive dipstick for leukocyte esterase and/or nitrate; b. pyuria (urine specimen with > 10 white blood cells /mm or > 3 white blood cells per field of unspun urine; or c. organisms seen on Gram’s stain of unspun urine. (3). Cellulitis or bone/joint infection is defined as erythema, pain, swelling, warmth of the affected skin or joints and limited movement. (4). Abdominal infection is defined as > 1 of following criteria: a. abdominal distension and tenderness, or local discomfort or peritonism; b. abdominal mass, e.g. gall bladder, pseudocyst, abscess; c. failure to tolerate enteral feed or nasogastric aspirates > 200ml/4hrly; d. diarrhoea; e. laparotomy for perforation or obstruction; f. pancreatitis, or cholecyctitis, or gynaecological infection, or pyelonephritis; g. abdominal collection shown on CT, ultrasound or abdominal X-ray. (5). Meningitis is defined as > 1 of following criteria: a. headache with stiff neck; b. focal neurological signs; c. LP positive; d. CT: raised ICP is suspected. (6). Endocarditis: fever and changing murmur are signs of suspected endocarditis. (7). Catheter or device infection: localised cellulitis. C. > 2 of the following signs of systemic inflammation in response to infection: (1). Core temperature: > 38.3C or 90 bpm, except in patients with a known medical condition to increase the heart rate or those receiving treatment that would prevent tachycardia; (3). Systolic BP 20 breaths /min or a PaCO2 26.8 kPa; (7). Ileus (absent bowel sounds); (8). Altered mental status; (9). Significant oedema or positive fluid balance (> 20 ml/kg over 24 hrs); (10). White cell count: > 12 000/mm or 10% immature neutrophils; (11). C-reactive protein > 2 SD above the normal value; (12). Plasma glucose > 7.7 mmol/l in the absence of diabetes; (13). Platelets count 49, 000/µl, or INR > 1.5 or APTT > 60s; (14). Plasma lactate > 2 mmol/l; (15). Bilirubin > 40, but 120, but =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Signs of severe sepsis: septic patients with any one of the following signs: (1). PaO2/FiO2 0.1 µg/kg/min; (3). Creatinine > 330 µmol/L; (4). Platelets 102 µmol/L; (6). Glasgow Coma Score 3 times the upper limit of laboratory normal ranges; • Pregnancy, breast-feeding or women of childbearing potential not using adequate contraception; • Previous adverse reaction to statins; • Concomitant use of fibrates or other lipid-lowering therapy; • Administration of atorvastatin was ceased <2 weeks prior to the trial (wash-out period in healthy volunteers: 7 days); • Concomitant use of erythromycin, telithromycin, clarithromycin itraconazole, imidazoles, triazoles, ciclosprin or grapefruit juice21; • Participation in another clinical trial; • Patients with terminal cancer; • Fail to obtain written consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To investigate the difference in rates of sepsis converting to severe sepsis and of Critical Care admissions between statin-treatment and placebo groups; 2. To look at the difference in rates of sepsis converting to severe sepsis and of Critical Care admissions amongst statin-treatment, placebo and pre-treated statins groups; 3. To evaluate the difference in hospital mortality rate between statin-treatment and placebo groups after the primary endpoint has been reached. ;Secondary Objective: ;Primary end point(s): The primary endpoint is sepsis converting to severe sepsis. The treatment with Atorvastatin will be discontinued after the patient has been found to have one or more of the signs of organ dysfunction (defined as severe sepsis). Organ dysfunction is defined Sequential Organ Failure Assessment (SOFA) Score > 3 within 24 hrs, which includes: (1). PaO2/FiO2 0.1 µg/kg/min; (3). Creatinine > 330 µmol/L; (4). Platelets 102 µmol/L; (6). Glasgow Coma Score < 9. | — |
Countries
United Kingdom
Outcome results
None listed