Severe SepsisPhase 3SartSepNCT01992796
Angiotensin II Antagonist in Severe Sepsis
A Phase 3 study testing Irbesartan in people with Severe Sepsis, run by University of Salerno at 1 site in Italy.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Severe Sepsis
- What is being tested?
- Irbesartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2014to Jan 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
Rosalba Tufano, MD contact
Ornella Piazza, MD contact
About this study
Official title: Phase III Study of Irbersartan for the Early Treatment of Severe Sepsis Patients
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.
Read the 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
- Being tested
- Irbesartan
- Keywords
- irbesartan, angiotensin, sepsis
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrbesartanDrug
Also called Candesartan., Telmisartan., Olmesartan., Lortaan
75 mg/per os/for 15 days
| Study group | Role | What they receive |
|---|---|---|
| irbesartan | Experimental | 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 Receives: Drug: Irbesartan |
| Placebo | Placebo comparator | Packaging and labelling for blinding purposes: tablets of placebo looking like the study drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
mortality
Measured: 28 days
Secondary outcomes (1)
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).
Measured: 28 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionJan 2017 (estimated)
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Salerno
- Sponsor type
- University, hospital or other
- Collaborators
- Federico II University
- Responsible party
- Principal investigator, Ornella Piazza, University of Salerno
- Investigators
- Rosalba Tufano, MD, Study director, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01992796
- Sponsor's protocol ID
- FARM97AJNN
- Acronym
- SartSep
- Status last verified
- Nov 2013
- First submitted
- 11 Nov 2013
- Last updated
- 25 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Irbersartan for the Early Treatment of Severe Sepsis Patients
- ClinicalTrials.gov ID
- NCT01992796
- Acronym / sponsor ID
- SartSep / FARM97AJNN
- Conditions
- Severe Sepsis
- Keywords
- irbesartan, angiotensin, sepsis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of SalernoUniversity, hospital or other
- Collaborators
- Federico II University
- Study start
- Jan 2014
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| irbesartan | Experimental | Drug: IrbesartanIrbesartan (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 |
| Placebo | Placebo comparator | –Packaging and labelling for blinding purposes: tablets of placebo looking like the study drug |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IrbesartanAlso: Candesartan., Telmisartan., Olmesartan., Lortaan75 mg/per os/for 15 days | Drug | irbesartan |
Primary outcome
mortality
Time frame: 28 days
1 secondary outcome
Incidence of altered organ function in sepsis patients measured by SOFA score (Sequential Organ Failure Assessment score)
Time frame: 28 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rosalba Tufano, MD contact
Ornella Piazza, MD contact
Rosalba Tufano, MD study director
Federico II University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Irbesartan in people with Severe Sepsis, run by University of Salerno at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rosalba Tufano, MD (rtufano@unina.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mortality (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2013.