Intravenous Clarithromycin in Septic Syndrome

Sepsis Clinical Trial

Official title:

Clarithromycin as Immunomodulatory Therapy for the Management of Septic Syndrome by Ventilator-Associated Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00297674
• Other study ID #: ACA-GREC-2004-01
• Status: Completed
• Phase: Phase 4
• First received: February 27, 2006
• Last updated: February 27, 2006
• Start date: June 2004
• Est. completion date: December 2005

Study information

• Verified date: July 2004
• Source: University of Athens
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. written informed consent provided by first or second degree relatives;

2. intubation and mechanical ventilation at least 48 hours prior to enrolment; c) age of patients equal to or more than 18 years;

d) diagnosis of Ventilator Associated Pneumonia; and e) signs of sepsis

Exclusion Criteria:

1. neutropenia, defined as less than 500 neutrophils/mm3;

2. HIV infection;

3. oral intake of corticosteroids at a dose equal to or higher than 1mg/kg equivalent prednisone for a period greater than one month;

4. administration of drotrecogin alpha the last five days prior to enrolment; and e) atrioventricular block of second or third degree.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Sepsis
• Systemic Inflammatory Response Syndrome
• Ventilator Associated Pneumonia

Intervention

Drug:
• Intravenous Clarithromycin

Locations

Country	Name	City	State
Greece	1st Department of Critical Care, Evangelismos General Hospital	Athens
Greece	2nd Department of Critical Care, ATTIKON University Hospital	Athens
Greece	4th Department of Internal Medicine, ATTIKON University Hospital	Athens

Sponsors (1)

Lead Sponsor	Collaborator
University of Athens

Country where clinical trial is conducted

Greece, 

References & Publications (3)

Giamarellos-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. — View Citation

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. — View Citation

Giamarellos-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimation of crude mortality by any reason of each study group
Primary	Estimation of attributable mortality by VAP of each study group
Primary	7-day mortality rate of each group
Primary	28-mortality rate of each group
Primary	Rate of progression to multiple organ failure and septic shock (and number of failing organs) of each study group
Primary	Time to progression to multiple organ failure and septic shock of each study group
Primary	Days of resolution of VAP
Primary	Days in ICU after diagnosis of VAP
Secondary	Influence of administration of clarithromycin on systemic inflammatory response