Clarithromycin as Immunomodulator for the Management of Sepsis

NCT01223690 | Completed Phase 3 DMC

• 1 other identifier: A06-269
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 6

Brief Summary

The herein protocol is based on the results of one former clinical trial conducted by our study group showing the considerable efficacy of intravenously administered clarithromycin as an adjuvant to antimicrobial chemotherapy for patients with sepsis, septic shock and respiratory failure in the field of ventilator-associated pneumonia. The proposed clinical trial is based on the need to generalize the application of intravenous clarithromycin in the total of admitted septic patients irrespective of the underlying cause of sepsis.

Conditions

Sepsis; Severe Sepsis; Septic Shock

Keywords

sepsis; infection; bacteremia; clarithromycin

Outcome Measures

Primary Outcomes (1)

• Effect of clarithromycin in mortality and risk for death by severe sepsis/shock and multiple organ dysfunction compared with placebo

  Survival analysis for 28 days will be done between placebo-treated patients and clarithromycin-treated patients separately for patients with sepsis; for patients with severe sepsis; and for patients with septic shock. Odds ratios for death by septic shock and/or multiple organ dysfunction will be assessed separately for each arm. Comparison of odds ratios will be done.

  28 days

Secondary Outcomes (4)

• Effect of clarithromycin compared with placebo in time to resolution of infection

  28 days

• Effect of clarithromycin compared with placebo in time to resolution of sepsis

  28 days

• Effect of clarithromycin compared with placebo in time to progression to severe sepsis or septic shock and multiple organ failure

  28 days

• Influence of administration of clarithromycin compared with placebo on systemic inflammatory response

  10 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

250 ml of dextrose 5% administered intravenously within one hour of continuous infusion for four consecutive days

Drug: Dextrose 5%

Clarithromycin

ACTIVE COMPARATOR

1000 mg of clarithromycin diluted in 250 ml of dextrose 5% administered intravenously within one hour of continuous infusion for four consecutive days

Drug: Clarithromycin

Interventions

Clarithromycin DRUG

1000 mg diluted into 250 ml of dextrose 5% administered intravenously within one hour of continuous infusion for four consecutive days

Also known as: Klaricid IV

Clarithromycin

Dextrose 5% DRUG

1000 mg diluted into 250 ml of dextrose 5% administered intravenously within one hour of continuous infusion for four consecutive days

Also known as: Dextrose solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One or more of the following infections: a) primary or secondary bacteremia by Gram-negative bacteria, b) acute pyelonephritis, or c) intrabdominal infection. Only one episode of infection per patient will be enrolled. Both patients with community-acquired and nosocomial infections are eligible for the study.
• The presence of at least two of the following criteria of sepsis according to ACCP/SCCM (8) a) body temperature \>38 degreesC or \<36 degreesC; b) pulse rate \>90/min; c) breath rate \>20/min or Pco2\<32mmHg; and/or d) leukocytosis (white blood cell count \>12,000/μl) or leukopenia (white blood cell count \<4,000/μl) or \>10% band forms

You may not qualify if:

• Presence of HIV infection
• Intake of corticosteroids at a dose more than or equal to 1mg/kg of equivalent prednisone for more than one month
• Neutropenia as \<500 neutrophils/μl
• Selection by the attending physician of a macrolide as empiric antimicrobial therapy for the infection making the patient eligible for the study

Sponsors & Collaborators

• University of Athens: lead

Study Sites (6)

3rd Department of Critical Care Medicine, National and Kapodistrian University of Athens

Athens, 11528, Greece

Location

2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens

Athens, 12462, Greece

Location

4th Department of Internal Medicine, National and Kapodistrian University of Athens

Athens, 12462, Greece

Location

2nd Department of Medicine, Sismanogleion General Hospital

Athens, 15126, Greece

Location

1st Department of Medicine, University of Patras

Pátrai, 24100, Greece

Location

2nd Department of Surgery, University of Thessaloniki

Thessaloniki, 54635, Greece

Location

Related Publications (8)

• Giamarellos-Bourboulis EJ. Macrocycle molecules for the management of systemic infections: the clarithromycin paradigm. Curr Top Med Chem. 2010;10(14):1470-5. doi: 10.2174/156802610792232033.

  PMID: 20536418 BACKGROUND

• Giamarellos-Bourboulis EJ, Pechere JC, Routsi C, Plachouras D, Kollias S, Raftogiannis M, Zervakis D, Baziaka F, Koronaios A, Antonopoulou A, Markaki V, Koutoukas P, Papadomichelakis E, Tsaganos T, Armaganidis A, Koussoulas V, Kotanidou A, Roussos C, Giamarellou H. Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia. Clin Infect Dis. 2008 Apr 15;46(8):1157-64. doi: 10.1086/529439.

  PMID: 18444850 BACKGROUND

• Giamarellos-Bourboulis EJ, Tziortzioti V, Koutoukas P, Baziaka F, Raftogiannis M, Antonopoulou A, Adamis T, Sabracos L, Giamarellou H. Clarithromycin is an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2006 May;57(5):937-44. doi: 10.1093/jac/dkl084. Epub 2006 Mar 20.

  PMID: 16549515 BACKGROUND

• 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.

  PMID: 14693524 BACKGROUND

• Vittoros 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.

  PMID: 34871241 DERIVED

• Karakike 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.

  PMID: 31783881 DERIVED

• Gainaru G, Papadopoulos A, Tsangaris I, Lada M, Giamarellos-Bourboulis EJ, Pistiki A. Increases in inflammatory and CD14dim/CD16pos/CD45pos patrolling monocytes in sepsis: correlation with final outcome. Crit Care. 2018 Mar 3;22(1):56. doi: 10.1186/s13054-018-1977-1.

  PMID: 29499723 DERIVED

• Antonakos N, Tsaganos T, Oberle V, Tsangaris I, Lada M, Pistiki A, Machairas N, Souli M, Bauer M, Giamarellos-Bourboulis EJ. Decreased cytokine production by mononuclear cells after severe gram-negative infections: early clinical signs and association with final outcome. Crit Care. 2017 Mar 9;21(1):48. doi: 10.1186/s13054-017-1625-1.

  PMID: 28274246 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic; Infections; Bacteremia

Interventions

Clarithromycin

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Evangelos Giamarellos-Bourboulis, MD, PhD

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Helen Giamarellou, MD, PhD

  National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

• Apostolos Armaganidis, MD

  National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

• George Koratzanis, MD

  Sismanogleion Athens General Hospital

  PRINCIPAL INVESTIGATOR

• Charalambos Gogos, MD, PhD

  University of Patras

  PRINCIPAL INVESTIGATOR

• Konstantinos Atmatzidis, MD

  University of Thessaloniki

  PRINCIPAL INVESTIGATOR

• Emmanouel Douzinas, MD, PhD

  National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 18, 2010
• First Posted: October 19, 2010
• Study Start: July 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: April 1, 2011
• Last Updated: August 4, 2011

Record last verified: 2010-10

Locations

GR (6)