Angiotensin II Antagonist in Severe Sepsis

Severe Sepsis Clinical Trial

— SartSep  

Official title:

Phase III Study of Irbersartan for the Early Treatment of Severe Sepsis Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01992796
• Other study ID #: FARM97AJNN
• Status: Not yet recruiting
• Phase: Phase 3
• First received: November 11, 2013
• Last updated: November 19, 2013
• Start date: January 2014
• Est. completion date: January 2017

Study information

• Verified date: November 2013
• Source: University of Salerno
• Contact: Rosalba Tufano, MD
• Email: rtufano[@]unina.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria: 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.

Exclusion Criteria:Patients already treated with ACE inhibitors or ARBs will be excluded. Patients admitted in shock conditions (systolic blood pressure lower than 90 mmHg) will be excluded. Patients with severe renal failure (serum creatinine of 2.0 mg/dL or dialysis) will be excluded.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Severe Sepsis
• Toxemia

Intervention

Drug:
• Irbesartan
75 mg/per os/for 15 days

Locations

Country	Name	City	State
Italy	Università di Salerno	Salerno

Sponsors (2)

Lead Sponsor	Collaborator
University of Salerno	Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of renal failure	Creatinine (mg/dl) (SOFA score) 1.2 - 1.9 (1) 2.0 - 3.4 (2) 3.5 - 4.9 (or urine output< 500 ml/d) (3) > 5.0 (or urine output< 200 ml/d) (4)	28 days	Yes
Primary	mortality		28 days	No
Secondary	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).	28 day	No