The trial investiges if the early administration of the glucocorticoid hydrocortisone in low doses prevents the development of cardiovascular c0llaps (shock) in patients with severe sepsis who are not in shock.
- Conditions
- Patients with severe sepsisMedDRA version: 16.1Level: PTClassification code 10040047Term: SepsisSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2007-004401-10-DE
- Lead Sponsor
- Charité Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 380
Patients must meet ALL inclusion criteria:
1.Informed consent from patient, legal representative, proxy, or independent medical consultant.
2.In women with child bearing potential an effective contraception with a failure rate < 1 %.
3.Clinical evidence of INFECTION (may be present = 48 hours) –
At least one of a-d is required.
a.Pathogenic micro-organism in blood, sputum, urine, or normally sterile body fluid
b.Identified focus of infection (e.g. ruptured bowel, purulent drainage or sputum)
c.Presence of granulocytes in normally sterile body fluid
d.Clinically suspected infection without positive culture of pathogenic microorganism (e.g. new infiltrate in chest X-ray, treated pneumonia, necrotizing fasciitis, purpura fulminans)
4.Evidence of SIRS (may be present = 48 hours) –
At least two of a-d are required.
a.Fever (=38 °C) or Hypothermia (= 36 °C)
b.Tachycardia (= 90 bpm)
c.Tachypnea (= 20 bpm) or hyperventilation (PaCO2 = 33 mmHg [= 4.3 kPa], or mechanical ventilation
d.Leukocytosis (= 12.000 / µl) or leukopenia (= 4.000 / µl) or = 10 % immature forms
5.Evidence of ORGAN DYSFUNCTION (may NOT be present = 48 hours –
At least one organ dysfunction of a-e is required
a.Encephalopathy: Reduced vigilance, disorientation, agitation, delirium etc. in the absence of psychotropic drugs
b.Acute renal dysfunction: Oliguria: = 0.5 ml/kg/h = 2 h despite adequate volume replacement and/or creatinine increase > 2 x above the normal upper range, and/or need for renal replacement therapy.
c.Coagulation dysfunction: Platelets = 100.000/µl or more than 30 % decrease from baseline within 24 hours. Thrombocytopenia may not be due to haemorrhage or immunologically induced.
d.Pulmonary dysfunction/hypoxemia: PaO2 = 75 mmHg [= 10 kPa] at room air or PaO2/FiO2 = 250 mmHg [= 33 kPa] with oxygen application. Hypoxemia may not be due to primary cardiac or pulmonary dysfunction (e.g. emphysema)
e.Microcirculatory dysfunction: Lactate > 1.5 x above the normal upper range and/or base deficit = 5 mmol/l and/or metabolic acidosis with pH < 7.3 and/or depressed capillary refill/mottling and/or significant body edema (capillary leakage syndrome)
A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on the contraceptive should be addressed [ICH-ORG 1995]
Due to the severity of the disease and hospitalisation, sexual abstinence during application of the study medication is assumed and may be regarded as an effective method of contraception, even if the investigator is not aware of an alternative mode of applied contraceptive method at the time of inclusion into the study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 230
Patients will be excluded for ANY ONE of the following reasons:
I.Sepsis-induced HYPOTENSION despite adequate volume replacement defined as a mean arterial pressure (MAP) < 65 mmHg or a systolic arterial pressure (SAP) < 90 mmHg, or the use of vasopressors to keep MAP = 65 mmHg or SAP = 90 mmHg, IF any of these conditions persist for 4 hours ore more.
NOTE: Patients who received transiently vasopressors only during initial resuscitation (volume deficit) or had an iatrogenic-induced hypotension (e.g. intubation, bolus sedation), but are free of vasopressors and have no hypotension for at least two hours after initial resuscitation or the hypotensive event, are defined to be not in shock. It is essential that at the time of allocation of study medication, patients MAY NOT be in septic shock.
Adequate volume status is defined as a central venous pressure = 8 mmHg in non-ventilated and = 12 mmHg in ventilated patients, and a central venous oxygen saturation = 70 %.
Vasopressor is defined as dopamine = 5 µg/kg/min or any dose of epinephrine, norepinephrine, vasopressin, or other vasopressor.
II.Patients with known hypersensitivity to hydrocortison-21-hydrogensuccinate, natrium-monohydrogenphosphate , or mannitol (placebo).
III.Patients who have a glucocorticoid history AND in whom a continued glucocorticoid therapy may be indicated (e.g. > 10 mg prednisolone equivalent per day for at least 5 days within the last 3 months). Topical or inhaled glucocorticoids are NO exclusion criteria, unless there is an indication for continued systemic glucocorticoid administration.
IV.Other indications for systemic glucocorticoid therapy (e.g. asthma, COPD, anaphylaxis, autoimmune diseases)
V.DNR-order
VI.Moribund patients
VII.Pregnancy (positive pregnancy test in women with child bearing potential)
VIII.Breast feeding women
IX.Age < 18 years
X.Concomitant or previous (within the last 30 days) participation in an other interventional clinical trial
XI.Relationship to the investigator (e.g. relatives, colleagues, staff)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method