The investigators propose a clinical study of irbersartan for the early treatment of severe sepsis patients with elevated predicted risk of death between. This study will evaluate whether early administration of the the angiotensin receptor blocker irbersartan provides significant reduction of 28 days mortality and multi organ failure incidence to patients with severe sepsis.
Background: Angiotensin II (ANG II) is a potent vasoconstrictor and diminishes vasodilator responses in arteries. In addition to direct effects on vascular tone, ANG II affects multiple aspects of microvascular function through promotion of leukostasis, induction of capillary permeability and depletion of glutathione. Binding of ANG II to its receptors (in particular AT1) mediates intracellular free radical generation that contributes to tissue damage by promoting mitochondrial dysfunction. Angiotensin receptor blockers (ARBs) interrupt renin-angiotensin system (RAS) overactivity by blocking a specific receptor that mediates the pathogenic activity of angiotensin II. Objectives: The clinical question objective of this study is if the antiinflammatory effect of ARBs is relevant in sepsis management and in particular if ARBs are able to improve survival and reduce the incidence of Multi Organ Failure in septic patients. Methods: STUDY DESIGN: Experimental; prospective, randomized, multicenter, phase III trial. STUDY POPULATION: Three hundred adults within 12 hrs of recognition of severe sepsis, with Acute Physiology and Chronic Health Evaluation (APACHE) II-predicted risk of mortality between 20% and 80% are eligible. Settings: 5 Italian Intensive Care Units. Oral irbesartan (total dose of 75 mg) or placebo administered every 24 hrs for 15 days. Analysis of data performed by a blind operator. Expected results: about 25% reduction in 28-day mortality rate and incidence of multi organ failure in the study population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
300
75 mg/per os/for 15 days
Università di Salerno
Salerno, Italy
mortality
Time frame: 28 days
Incidence of altered organ function in sepsis patients measured by SOFA score (Sequential Organ Failure Assessment score)
Incidence of altered organ function in sepsis patients measured by SOFA score (Sequential Organ Failure Assessment score). It is known that respiratory failure is more common in the first 72 hours after the original insult, hepatic failure after 5-7 days, gastrointestinal bleeding within 10-15 days and renal failure in 11-17 days: the SOFA score will be checked every day for 28 days. The SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Creatinine serum levels, bilirubin, coagulation tests, blood gases and neurological clinical evaluation will be performed every day for the first 15 days; they will be retested at least once a week and at the end of the study protocol (28-day).
Time frame: 28 day
Ornella Piazza, MD
CONTACT
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