Angiotensin II Antagonist in Severe Sepsis

NCT ID: NCT01992796

Last Updated: 2013-11-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2017-01-31

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.

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.

Conditions

Severe Sepsis

Keywords

irbesartan, angiotensin, sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Irbesartan

Intervention Type: DRUG

75 mg/per os/for 15 days

Placebo

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

Group Type: PLACEBO_COMPARATOR

No interventions assigned to this group

Interventions

Irbesartan

75 mg/per os/for 15 days

Intervention Type: DRUG

Other Intervention Names

Candesartan.; Telmisartan.; Olmesartan.; Lortaan; Losaprex; Neolotan; Tevetenz; Rixil; Tareg; Valpression; Aprovel; Karvea.

Eligibility Criteria

Inclusion 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: collaborator

University of Salerno

OTHER

Sponsor Role: lead

Responsible Party

Ornella Piazza

Reasercher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rosalba Tufano, MD

Role: STUDY_DIRECTOR

Federico II University

Locations

Università di Salerno

Salerno, , Italy

Countries

Italy

Central Contacts

Rosalba Tufano, MD

Role: CONTACT

Email: rtufano@unina.it

Ornella Piazza, MD

Role: CONTACT

Facility Contacts

Ornella Piazza

Role: primary

Other Identifiers

FARM97AJNN

Identifier Type: -

Identifier Source: org_study_id