Randomised Double-Blind Placebo Controlled Trial of 40mg/day of Atorvastatin on Reduction in Severity of Sepsis in Ward Patients - Clinical trial of Atorvastatin on Reduction in Severity of Sepsis

• Conditions: 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.

• Registration Number: EUCTR2005-004636-52-GB
• Lead Sponsor: Heart of England NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-11-24
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 414

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 < 36C;

(2). Heart rate: > 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 < 90 mmHg, or MAP < 70 mmHg;

(4). Decreased capillary refill or mottling;

(5). Urine output < 0.5 ml/kg/h for more than 2 hrs;

(6). Respiratory rate: > 20 breaths /min
or a PaCO2 < 4.3 or PaO2/FiO2 < 40, but > 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 < 4000/mm
or a differential count showing >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 <100,000, but > 49, 000/µl, or INR > 1.5 or APTT > 60s;

(14). Plasma lactate > 2 mmol/l;

(15). Bilirubin > 40, but < 101 µmol/l;

(16). Creatinine > 120, but < 177 µmol/l.

Are the trial subjects under 18? no
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

• Signs of severe sepsis: septic patients with any one of the following signs:
(1). PaO2/FiO2 < 26.7 kPa;
(2). Noradrenaline/adrenaline > 0.1 µg/kg/min;
(3). Creatinine > 330 µmol/L;
(4). Platelets <50 x 103/ mL;
(5). Bilirubin > 102 µmol/L;
(6). Glasgow Coma Score < 9.

• Known active liver disease, alcohol abuse
or persistently abnormal liver function tests:
alanine aminotransferase, or creatine kinase > 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.

Study & Design

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