Angiotensin II Antagonist in Severe Sepsis (SartSep)
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|ClinicalTrials.gov Identifier: NCT01992796|
Recruitment Status : Unknown
Verified November 2013 by Ornella Piazza, University of Salerno.
Recruitment status was: Not yet recruiting
First Posted : November 25, 2013
Last Update Posted : November 25, 2013
|Condition or disease||Intervention/treatment||Phase|
|Severe Sepsis||Drug: Irbesartan||Phase 3|
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.
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 (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Phase III Study of Irbersartan for the Early Treatment of Severe Sepsis Patients|
|Study Start Date :||January 2014|
|Estimated Primary Completion Date :||January 2017|
|Estimated Study Completion Date :||January 2017|
Irbesartan (total dose of 75 mg) or placebo administered every 24 hrs for 15 days. Moreover, the sepsis management will follow standard international guidelines (Crit Care Med.2008 Jan;36(1):296-327. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock).
Duration of treatment: Irbesartan 75 mg daily for 15 days; only one cycle. Follow up will last 90 days both for treatment and control arm.
all the therapeutic interventions for sepsis management as indicated by international guidelines are admitted. During the trial are not permitted: ACE inhibitors, ARBs different from Irbersartan, angiotensin I synthesis inhibitors
75 mg/per os/for 15 days
Placebo Comparator: Placebo
Packaging and labelling for blinding purposes: tablets of placebo looking like the study drug
- mortality [ Time Frame: 28 days ]
- Incidence of altered organ function in sepsis patients measured by SOFA score (Sequential Organ Failure Assessment score) [ Time Frame: 28 day ]
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).
- Incidence of renal failure [ Time Frame: 28 days ]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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01992796
|Contact: Rosalba Tufano, MDfirstname.lastname@example.org|
|Contact: Ornella Piazza, MD|
|Università di Salerno|
|Contact: Ornella Piazza|
|Principal Investigator: Ornella Piazza|
|Study Director:||Rosalba Tufano, MD||Federico II University|