SepsisPhase 4NCT00297674
Intravenous Clarithromycin in Septic Syndrome
A Phase 4 study testing Intravenous Clarithromycin in people with Sepsis and Ventilator Associated Pneumonia, run by University of Athens at 3 sites in Greece.
Trial summary
The aim of this clinical trial is to clarify the clinical efficacy of clarithromycin as immunotherapy for the management of septic syndrome by ventilator-associated pneumonia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Ventilator Associated Pneumonia
- What is being tested?
- Intravenous Clarithromycin
- Type of treatment
- Injection or infusion
- How many people
- 200 participants
- Where
- 3 sitesGreece
- Study dates
- Jun 2004to Dec 2005
- Phase
- Phase 4
- 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
- written informed consent provided by first or second degree relatives;
- intubation and mechanical ventilation at least 48 hours prior to enrolment; c) age of patients equal to or more than 18 years;
- diagnosis of Ventilator Associated Pneumonia; and e) signs of sepsis
Who cannot join
- neutropenia, defined as less than 500 neutrophils/mm3;
- HIV infection;
- oral intake of corticosteroids at a dose equal to or higher than 1mg/kg equivalent prednisone for a period greater than one month;
- administration of drotrecogin alpha the last five days prior to enrolment; and e) atrioventricular block of second or third degree.
Trial locations and contacts
3 sites in 1 country.
Greece3 sites
1st Department of Critical Care, Evangelismos General Hospital
Athens, 106 72
2nd Department of Critical Care, ATTIKON University Hospital
Athens, 124 64
4th Department of Internal Medicine, ATTIKON University Hospital
Athens, 124 64
About this study
Official title: Clarithromycin as Immunomodulatory Therapy for the Management of Septic Syndrome by Ventilator-Associated Pneumonia
The aim of this clinical trial is to clarify the clinical efficacy of clarithromycin as immunotherapy for the management of septic syndrome by ventilator-associated pneumonia.
Read the detailed description
The rationale of the trial is based on the favorable results of experimental studies of sepsis by multidrug-resistant Pseudomonas aeruginosa and by susceptible Escherichia coli in rabbits where clarithromycin was administered intravenously. Data from these latter studies suggest that administration of clarithromycin extended survival and attenuated systemic inflammatory response. Their major endpoint was successful immunotherapy achieved when clarithromycin was administered on presentation of symptoms of sepsis-induced pulmonary edema; on the contrary, former clinical trials for immunotherapies of sepsis were based on animal studies where the under evolution immunomodulator was administered before bacterial challenge. The efficacy of administration of clarithromycin upon presentation of septic syndrome in animal studies, renders its application promising in the clinical field.
- Conditions
- Sepsis, Ventilator Associated Pneumonia
- Being tested
- Intravenous Clarithromycin
- Keywords
- clarithromycin, sepsis, immunomodulation
- Medical subject headings
- Sepsis, Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous ClarithromycinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimation of crude mortality by any reason of each study group
Estimation of attributable mortality by VAP of each study group
7-day mortality rate of each group
28-mortality rate of each group
Rate of progression to multiple organ failure and septic shock (and number of failing organs) of each study group
Time to progression to multiple organ failure and septic shock of each study group
Days of resolution of VAP
Days in ICU after diagnosis of VAP
Secondary outcomes (1)
Influence of administration of clarithromycin on systemic inflammatory response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2006 (estimated)
- Study startJun 2004
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 200 participants
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Investigators
- Evangelos J Giamarellos-Bourboulis, MD, PhD, Study chair, University of Athens, Medical School, GreeceHelen Giamarellou, MD, PhD, Principal investigator, University of Athens, Medical School, GreeceApostolos Armaganidis, MD, PhD, Principal investigator, University of Athens, Medical School, GreeceCharis Roussos, MD, PhD, Principal investigator, University of Athens, Medical School, Greece
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00297674
- Sponsor's protocol ID
- ACA-GREC-2004-01
- Status last verified
- Jul 2004
- First submitted
- 27 Feb 2006
- Last updated
- 28 Feb 2006
- Results posted
- No
Publications
Giamarellos-Bourboulis EJ, Adamis T, Laoutaris G, Sabracos L, Koussoulas V, Mouktaroudi M, Perrea D, Karayannacos PE, Giamarellou H. Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2004 Jan;48(1):93-9. doi: 10.1128/AAC.48.1.93-99.2004.
PubMed 14693524Giamarellos-Bourboulis EJ, Baziaka F, Antonopoulou A, Koutoukas P, Kousoulas V, Sabracos L, Panagou C, Perrea D, Giamarellou H. Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli. Int J Antimicrob Agents. 2005 Feb;25(2):168-72. doi: 10.1016/j.ijantimicag.2004.08.018.
PubMed 15664488Giamarellos-Bourboulis E, Adamis T, Sabracos L, Raftogiannis M, Baziaka F, Tsaganos T, Koutoukas P, Plachouras D, Karayannacos P, Giamarellou H. Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli. Scand J Infect Dis. 2005;37(1):48-54. doi: 10.1080/00365540510026832.
PubMed 15764190Vittoros V, Kyriazopoulou E, Lada M, Tsangaris I, Koutelidakis IM, Giamarellos-Bourboulis EJ. Soluble fms-like tyrosine kinase 1, placental growth factor and procalcitonin as biomarkers of gram-negative sepsis: Analysis through a derivation and a validation cohort. Medicine (Baltimore). 2021 Nov 5;100(44):e27662. doi: 10.1097/MD.0000000000027662.
PubMed 34871241Karakike E, Kyriazopoulou E, Tsangaris I, Routsi C, Vincent JL, Giamarellos-Bourboulis EJ. The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort. Crit Care. 2019 Nov 29;23(1):387. doi: 10.1186/s13054-019-2665-5.
PubMed 31783881Strouvalis I, Routsi C, Adamopoulou M, Raftogiannis M, Renieris G, Orfanos SE, Kotanidou A, Sabracos L, Giamarellos-Bourboulis EJ. Early increase of VEGF-A is associated with resolution of ventilator-associated pneumonia: Clinical and experimental evidence. Respirology. 2018 Oct;23(10):942-949. doi: 10.1111/resp.13320. Epub 2018 May 9.
PubMed 29741298Tsaganos T, Raftogiannis M, Pratikaki M, Christodoulou S, Kotanidou A, Papadomichelakis E, Armaganidis A, Routsi C, Giamarellos-Bourboulis EJ. Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis. Antimicrob Agents Chemother. 2016 May 23;60(6):3640-6. doi: 10.1128/AAC.02974-15. Print 2016 Jun.
PubMed 27044546Giamarellos-Bourboulis EJ. Immunomodulatory therapies for sepsis: unexpected effects with macrolides. Int J Antimicrob Agents. 2008 Nov;32 Suppl 1:S39-43. doi: 10.1016/j.ijantimicag.2008.06.004. Epub 2008 Aug 15.
PubMed 18707849
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clarithromycin as Immunomodulatory Therapy for the Management of Septic Syndrome by Ventilator-Associated Pneumonia
- ClinicalTrials.gov ID
- NCT00297674
- Acronym / sponsor ID
- ACA-GREC-2004-01
- Conditions
- Sepsis, Ventilator Associated Pneumonia
- Keywords
- clarithromycin, sepsis, immunomodulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- Jun 2004
- Study completion
- Dec 2005
- First posted
- 28 Feb 2006 (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 aim of this clinical trial is to clarify the clinical efficacy of clarithromycin as immunotherapy for the management of septic syndrome by ventilator-associated pneumonia.
Detailed description
The rationale of the trial is based on the favorable results of experimental studies of sepsis by multidrug-resistant Pseudomonas aeruginosa and by susceptible Escherichia coli in rabbits where clarithromycin was administered intravenously. Data from these latter studies suggest that administration of clarithromycin extended survival and attenuated systemic inflammatory response. Their major endpoint was successful immunotherapy achieved when clarithromycin was administered on presentation of symptoms of sepsis-induced pulmonary edema; on the contrary, former clinical trials for immunotherapies of sepsis were based on animal studies where the under evolution immunomodulator was administered before bacterial challenge. The efficacy of administration of clarithromycin upon presentation of septic syndrome in animal studies, renders its application promising in the clinical field.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- written informed consent provided by first or second degree relatives;
- intubation and mechanical ventilation at least 48 hours prior to enrolment; c) age of patients equal to or more than 18 years;
- diagnosis of Ventilator Associated Pneumonia; and e) signs of sepsis
Key exclusion criteria (4 listed)
- neutropenia, defined as less than 500 neutrophils/mm3;
- HIV infection;
- oral intake of corticosteroids at a dose equal to or higher than 1mg/kg equivalent prednisone for a period greater than one month;
- administration of drotrecogin alpha the last five days prior to enrolment; and e) atrioventricular block of second or third degree.
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 |
|---|---|---|
| Intravenous Clarithromycin | Drug | – |
Primary outcome
Estimation of crude mortality by any reason of each study group
Estimation of attributable mortality by VAP of each study group
7-day mortality rate of each group
28-mortality rate of each group
Rate of progression to multiple organ failure and septic shock (and number of failing organs) of each study group
Time to progression to multiple organ failure and septic shock of each study group
Days of resolution of VAP
Days in ICU after diagnosis of VAP
1 secondary outcome
Influence of administration of clarithromycin on systemic inflammatory response
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2006.
- Background: PubMed 14693524Giamarellos-Bourboulis EJ, Adamis T, Laoutaris G, Sabracos L, Koussoulas V, Mouktaroudi M, Perrea D, Karayannacos PE, Giamarellou H. Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2004 Jan;48(1):93-9. doi: 10.1128/AAC.48.1.93-99.2004.
- Background: PubMed 15664488Giamarellos-Bourboulis EJ, Baziaka F, Antonopoulou A, Koutoukas P, Kousoulas V, Sabracos L, Panagou C, Perrea D, Giamarellou H. Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli. Int J Antimicrob Agents. 2005 Feb;25(2):168-72. doi: 10.1016/j.ijantimicag.2004.08.018.
- Background: PubMed 15764190Giamarellos-Bourboulis E, Adamis T, Sabracos L, Raftogiannis M, Baziaka F, Tsaganos T, Koutoukas P, Plachouras D, Karayannacos P, Giamarellou H. Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli. Scand J Infect Dis. 2005;37(1):48-54. doi: 10.1080/00365540510026832.
- Derived from this study: PubMed 34871241Vittoros V, Kyriazopoulou E, Lada M, Tsangaris I, Koutelidakis IM, Giamarellos-Bourboulis EJ. Soluble fms-like tyrosine kinase 1, placental growth factor and procalcitonin as biomarkers of gram-negative sepsis: Analysis through a derivation and a validation cohort. Medicine (Baltimore). 2021 Nov 5;100(44):e27662. doi: 10.1097/MD.0000000000027662.
- Derived from this study: PubMed 31783881Karakike E, Kyriazopoulou E, Tsangaris I, Routsi C, Vincent JL, Giamarellos-Bourboulis EJ. The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort. Crit Care. 2019 Nov 29;23(1):387. doi: 10.1186/s13054-019-2665-5.
- Derived from this study: PubMed 29741298Strouvalis I, Routsi C, Adamopoulou M, Raftogiannis M, Renieris G, Orfanos SE, Kotanidou A, Sabracos L, Giamarellos-Bourboulis EJ. Early increase of VEGF-A is associated with resolution of ventilator-associated pneumonia: Clinical and experimental evidence. Respirology. 2018 Oct;23(10):942-949. doi: 10.1111/resp.13320. Epub 2018 May 9.
- Derived from this study: PubMed 27044546Tsaganos T, Raftogiannis M, Pratikaki M, Christodoulou S, Kotanidou A, Papadomichelakis E, Armaganidis A, Routsi C, Giamarellos-Bourboulis EJ. Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis. Antimicrob Agents Chemother. 2016 May 23;60(6):3640-6. doi: 10.1128/AAC.02974-15. Print 2016 Jun.
- Derived from this study: PubMed 18707849Giamarellos-Bourboulis EJ. Immunomodulatory therapies for sepsis: unexpected effects with macrolides. Int J Antimicrob Agents. 2008 Nov;32 Suppl 1:S39-43. doi: 10.1016/j.ijantimicag.2008.06.004. Epub 2008 Aug 15.
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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.
Evangelos J Giamarellos-Bourboulis, MD, PhD study chair
University of Athens, Medical School, Greece
Helen Giamarellou, MD, PhD principal investigator
University of Athens, Medical School, Greece
Apostolos Armaganidis, MD, PhD principal investigator
University of Athens, Medical School, Greece
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravenous Clarithromycin in people with Sepsis and Ventilator Associated Pneumonia, run by University of Athens at 3 sites in Greece.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 28 Feb 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Greece. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Estimation of crude mortality by any reason of each study group. The study lists 8 primary outcomes in all. 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 NCT00297674, which also lists 8 linked publications.
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 28 Feb 2006.