Systemic Inflammatory Response SyndromePhase 2NCT00708799
Efficacy of Macrolide Immunomodulation in Severe Sepsis.
A Phase 2 study testing Azithromycin on admission - not enrolled in the RCT in people with Systemic Inflammatory Response Syndrome, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The purpose of this study is to determine whether macrolide treatment of patients with severe sepsis has an advantageous immunomodulatory and clinical effect compared to severe septic patients without macrolide therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Inflammatory Response Syndrome
- What is being tested?
- Azithromycin on admission - not enrolled in the RCT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Nov 2013
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject, or legal representative, has given written informed consent.
- 18 years of age or older.
- SIRS is defined as two or more of:
- Temperature > 38o C or < 36oC
- Heart rate > 90 beats/min
- Respiratory rate > 20 breaths/min or PaCO2< 32mmHg
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- White blood cell count > 12.000/mm3; < 4000/mm3; or > 10% immature (band) forms.
- Presence of a suspected or proven infection. Patients with suspected infection must have evidence of an infection, such as white blood cells in a normally sterile body fluid, perforated viscus, chest x-ray consistent with pneumonia and associated with purulent sputum production, or a clinical syndrome associated with a high probability of infection (for example, purpura fulminans or ascending cholangitis).
- Presence of one or more sepsis-associated organ failure. The onset of the first sepsis-associated organ failure must occur within the 48-hour period immediately preceding initiation of study drug infusion. A patient must have an organ failure attributable to the sepsis episode. The organ failure must be newly developed and not explained by underlying disease processes or by effects of concomitant therapy.
- Cardiovascular: An arterial systolic blood pressure (SBP) of 90 mm Hg or a mean arterial pressure (MAP) 70 mm Hg for at least 1 hour despite adequate fluid resuscitation, adequate intravascular volume status, or the need for vasopressors to maintain SBP 90 mm Hg or MAP 70 mm Hg.
- Renal: Average urine output <0.5 mL/kg/h for 1 hour despite adequate fluid resuscitation
- Respiratory: Evidence of acute pulmonary dysfunction PaO2/FiO2 300 and, clinical exam or pulmonary capillary wedge pressure not suggestive of volume overload. If pneumonia is the suspected site of infection, the patient must have a PaO2/FiO2 200.
- Hematology: Platelet count <80,000/mm3 or a 50% decrease in platelet count from the highest value recorded over the last 3 days.
- Unexplained metabolic acidosis: Defined by (1) pH 7.30 or base deficit 5.0 mEq/L or (2) plasma lactate level >1.5 times the upper limit of normal.
- Adequate fluid resuscitation or adequate intravascular volume is defined as either pulmonary arterial wedge pressure 12 mm Hg or central venous pressure 8 mm Hg. Vasopressors is defined as dopamine 5 g/kg/min or any dose of norepinephrine, epinephrine, or phenylephrine. Dobutamine is not considered a vasopressor.
Who cannot join
- Macrolide therapy indicated for clinical condition. If after randomization, the treating physician determines that a macrolide is indicated and no other alternative antibiotic is appropriate, the patient will be excluded from the trial. However, if only one dose of azithromycin had been given and the treating physician decided to stop it, azithromycin might be administered.
- Known allergy to macrolides.
- Prolonged QT syndrome or on medications with increased risk of QT prolongation.
- Pregnant or lactating.
- Immunosuppression as defined by:
- Chemotherapy within the last 30 days,
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- Leukemia or lymphoma which is not in remission,
- Solid organ or bone marrow/stem cell transplant,
- Human Immunodeficiency Virus infection with CD4 count < 200 cells/mm3,
- Chronic corticosteroid use equivalent to > 10 mg prednisone per day,
- Patient or family decision to limit ICU care.
Trial locations and contacts
1 site in 1 country.
United States1 site
South Texas Health Care System, San Antonio, TX
San Antonio, Texas, 78229
About this study
Official title: Efficacy of Macrolide Immunomodulation in Severe Sepsis
The purpose of this study is to determine whether macrolide treatment of patients with severe sepsis has an advantageous immunomodulatory and clinical effect compared to severe septic patients without macrolide therapy. Our main hypothesis is macrolide use in addition to standard therapy in severe septic patients has an advantageous immunomodulatory and clinical effect compared to patients with severe sepsis not treated with a macrolide.
Read the detailed description
In recent studies, the significant effects of macrolide antibiotics (azithromycin) on immune response, unrelated to their anti-microbial properties, have been appreciated. Clinical trials of macrolides added to -lactams in bacteremic Streptococcus pneumoniae community-acquired pneumonia (CAP) have consistently demonstrated an absolute risk reduction in mortality of 15% in most populations. Several cytokines including tumor necrosis factor (TNF) interleukin (IL) -1 and IL-8 which are generally proinflammatory and IL-6 and IL-10, which tend to be anti-inflammatory have been associated with sepsis. TNF is a cytokine that for a number of reasons is thought to play a central role in the pathogenesis of sepsis and septic shock. TNF concentrations are increased during clinical and experimental sepsis and increasing concentrations and especially persistence of high concentrations of TNF during sepsis are associated with decreased survival. Therefore, our primary aim is to determine whether macrolide treatment of patients with severe sepsis has an advantageous immunomodulatory and clinical effect compared to severe septic patients without macrolide therapy. Our main hypothesis is macrolide use in addition to standard therapy in severe septic patients has an advantageous immunomodulatory and clinical effect compared to patients with severe sepsis not treated with a macrolide.
- Conditions
- Systemic Inflammatory Response Syndrome
- Being tested
- Azithromycin on admission - not enrolled in the RCT
- Medical subject headings
- Systemic Inflammatory Response Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin on admission - not enrolled in the RCTOther
Also called Arm 3
One dose of azithromycin prior to inclusion to the RCT
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Standard antibiotic therapy +Azithromycin 500 mg intravenously daily for 5 days Receives: Other: Azithromycin on admission - not enrolled in the RCT |
| Arm 2 | No intervention | Standard antibiotic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cytokines expression
Measured: Between admission and day five of treatment
Secondary outcomes (1)
28-day mortality
Measured: 28 days or discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2008 (estimated)
- Study startNov 2007
- Primary completionNov 2013
- Study completionNov 2013
Why it stopped: Safety evaluation due to recent publications.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Marcos I Restrepo, MD BA MSc, Principal investigator, South Texas Health Care System, San Antonio, TX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00708799
- Sponsor's protocol ID
- VISN 17-001
- Other IDs
- 5K23HL096054-03, UHS#20151
- Status last verified
- Apr 2017
- First submitted
- 27 Jun 2008
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Lopes Junior E, Leite HP, Pinho Franco MDC, Konstantyner T. Association of selenium status with endothelial activation during acute systemic inflammation in children. Clin Nutr ESPEN. 2022 Feb;47:367-374. doi: 10.1016/j.clnesp.2021.11.007. Epub 2021 Nov 14.
PubMed 35063229
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Macrolide Immunomodulation in Severe Sepsis
- ClinicalTrials.gov ID
- NCT00708799
- Acronym / sponsor ID
- VISN 17-001
- Conditions
- Systemic Inflammatory Response Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety evaluation due to recent publications.
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Northwestern University, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2007 (actual)
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 2 Jul 2008 (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 purpose of this study is to determine whether macrolide treatment of patients with severe sepsis has an advantageous immunomodulatory and clinical effect compared to severe septic patients without macrolide therapy. Our main hypothesis is macrolide use in addition to standard therapy in severe septic patients has an advantageous immunomodulatory and clinical effect compared to patients with severe sepsis not treated with a macrolide.
Detailed description
In recent studies, the significant effects of macrolide antibiotics (azithromycin) on immune response, unrelated to their anti-microbial properties, have been appreciated. Clinical trials of macrolides added to -lactams in bacteremic Streptococcus pneumoniae community-acquired pneumonia (CAP) have consistently demonstrated an absolute risk reduction in mortality of 15% in most populations. Several cytokines including tumor necrosis factor (TNF) interleukin (IL) -1 and IL-8 which are generally proinflammatory and IL-6 and IL-10, which tend to be anti-inflammatory have been associated with sepsis. TNF is a cytokine that for a number of reasons is thought to play a central role in the pathogenesis of sepsis and septic shock. TNF concentrations are increased during clinical and experimental sepsis and increasing concentrations and especially persistence of high concentrations of TNF during sepsis are associated with decreased survival. Therefore, our primary aim is to determine whether macrolide treatment of patients with severe sepsis has an advantageous immunomodulatory and clinical effect compared to severe septic patients without macrolide therapy. Our main hypothesis is macrolide use in addition to standard therapy in severe septic patients has an advantageous immunomodulatory and clinical effect compared to patients with severe sepsis not treated with a macrolide.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Other: Azithromycin on admission - not enrolled in the RCTStandard antibiotic therapy +Azithromycin 500 mg intravenously daily for 5 days |
| Arm 2 | No intervention | –Standard antibiotic therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subject, or legal representative, has given written informed consent.
- 18 years of age or older.
- SIRS is defined as two or more of:
- Presence of a suspected or proven infection. Patients with suspected infection must have evidence of an infection, such as white blood cells in a normally sterile body fluid, perforated viscus, chest x-ray consistent with pneumonia and associated with purulent sputum production, or a clinical syndrome associated with a high probability of infection (for example, purpura fulminans or ascending cholangitis).
- Presence of one or more sepsis-associated organ failure. The onset of the first sepsis-associated organ failure must occur within the 48-hour period immediately preceding initiation of study drug infusion. A patient must have an organ failure attributable to the sepsis episode. The organ failure must be newly developed and not explained by underlying disease processes or by effects of concomitant therapy.
Key exclusion criteria (11 listed)
- Macrolide therapy indicated for clinical condition. If after randomization, the treating physician determines that a macrolide is indicated and no other alternative antibiotic is appropriate, the patient will be excluded from the trial. However, if only one dose of azithromycin had been given and the treating physician decided to stop it, azithromycin might be administered.
- Known allergy to macrolides.
- Prolonged QT syndrome or on medications with increased risk of QT prolongation.
- Pregnant or lactating.
- Chemotherapy within the last 30 days,
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 |
|---|---|---|
| Azithromycin on admission - not enrolled in the RCTAlso: Arm 3One dose of azithromycin prior to inclusion to the RCT | Other | Arm 1 |
Primary outcome
Change in cytokines expression
Time frame: Between admission and day five of treatment
1 secondary outcome
28-day mortality
Time frame: 28 days or discharge
Results and safety
The study was stopped early (reason given: Safety evaluation due to recent publications.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
- Derived from this study: PubMed 35063229Lopes Junior E, Leite HP, Pinho Franco MDC, Konstantyner T. Association of selenium status with endothelial activation during acute systemic inflammation in children. Clin Nutr ESPEN. 2022 Feb;47:367-374. doi: 10.1016/j.clnesp.2021.11.007. Epub 2021 Nov 14.
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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.
Marcos I Restrepo, MD BA MSc principal investigator
South Texas Health Care System, San Antonio, TX
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azithromycin on admission - not enrolled in the RCT in people with Systemic Inflammatory Response Syndrome, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. 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: stopped early, as of the sponsor's last update on 21 Apr 2017. 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 United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Safety evaluation due to recent publications.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cytokines expression (time frame: Between admission and day five of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00708799, which also lists 1 linked publication.
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 21 Apr 2017.