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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
Sponsor:
Collaborator:
Federico II University
Information provided by (Responsible Party):
Ornella Piazza, University of Salerno

Brief 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.

Condition or disease Intervention/treatment Phase
Severe Sepsis Drug: Irbesartan Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis
Drug Information available for: Irbesartan

Arm Intervention/treatment
Experimental: irbesartan

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.

  • Route of administration : oral by nasogastric tube.
  • Medication permitted and not permitted during the trial:

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

Drug: Irbesartan
75 mg/per os/for 15 days
Other Names:
  • Candesartan.
  • Telmisartan.
  • Olmesartan.
  • Lortaan
  • Losaprex
  • Neolotan
  • Tevetenz
  • Rixil
  • Tareg
  • Valpression
  • Aprovel
  • Karvea.

Placebo Comparator: Placebo
Packaging and labelling for blinding purposes: tablets of placebo looking like the study drug



Primary Outcome Measures :
  1. mortality [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. 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).



Other Outcome Measures:
  1. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

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


Contacts
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Contact: Rosalba Tufano, MD rtufano@unina.it
Contact: Ornella Piazza, MD

Locations
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Italy
Università di Salerno
Salerno, Italy
Contact: Ornella Piazza         
Principal Investigator: Ornella Piazza         
Sponsors and Collaborators
University of Salerno
Federico II University
Investigators
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Study Director: Rosalba Tufano, MD Federico II University
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Responsible Party: Ornella Piazza, Reasercher, University of Salerno
ClinicalTrials.gov Identifier: NCT01992796    
Other Study ID Numbers: FARM97AJNN
First Posted: November 25, 2013    Key Record Dates
Last Update Posted: November 25, 2013
Last Verified: November 2013
Keywords provided by Ornella Piazza, University of Salerno:
irbesartan, angiotensin, sepsis
Additional relevant MeSH terms:
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Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Telmisartan
Candesartan
Olmesartan
Irbesartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action