Clarithromycin Treatment to Prevent Sepsis Progression in CAP (REACT)

NCT06294600 | Recruiting Phase 3

• 2 other identifiers: REACT2023-507295-40
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 24

Brief Summary

The primary objective of the REACT randomized clinical trial (RCT) is to optimize the clinical benefit from adjunctive clarithromycin treatment shown in the ACCESS trial and to provide evidence for the clinical benefit of early start of adjunctive oral clarithromycin guided by suPAR to prevent the progression into sepsis in patients with community-acquired pneumonia (CAP) at risk. This can be achieved by endpoints incorporating clinical benefit with the effect of treatment on the improvement of the immune dysregulation of CAP. The secondary objectives of REACT are to investigate the impact of early adjunctive treatment with clarithromycin on the resolution of CAP at the test-of-cure (TOC) visit.

Conditions

Community-acquired Pneumonia

Keywords

CAP; CLARITHROMYCIN; SEPSIS; suPAR; PCT; ACCESS; SOFA; RSS

Outcome Measures

Primary Outcomes (3)

• Change of baseline respiratory symptoms score

  At least 50 percent (%) decrease of the sum of scoring (0-12) for the symptoms of cough (0-3), dyspnea (0-3), purulent sputum expectoration (0-3) and pleuritic chest pain (0-3) between baseline and Study Day 4

  4 Days

• Change of baseline total sequential organ failure assessment (SOFA) score

  At least 30 percent (%) decrease between baseline sequential organ failure assessment (SOFA) score and measured sequential organ failure assessment (SOFA) score at Study Day 4.

  4 Days

• Change of baseline on both plasma PCT and plasma IL-10 or IL-8 to IL-10 ratio

  Plasma PCT on visit 4 has decreased by at least 80% from baseline PCT on screening or it is below 0.25 ng/ml AND (\[plasma IL-10 on visit 4 has decreased by at least 25% from IL-10 of visit 1 or it is below the lower limit of detection\] OR \[the IL-8 to IL-10 ratio of day 4 has decreased less than 15% from the IL-8 to IL-10 ratio of visit 1\]).

  4 Days

Secondary Outcomes (9)

• The number of patients that succeeded the resolution of CAP at the test of cure (TOC) visit.

  14 Days

• Need for up-escalation of the SoC administered antibiotics.

  28 Days

• Survival

  28 Days

• Change of baseline sequential organ failure assessment (SOFA) score

  8 Days

• Change of baseline on both plasma PCT and plasma IL-10 or IL-8 to IL-10 ratio

  8 Days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

These patients will be treated with 1 placebo tablet every 12 hours and it is suggested that all patients receive at least one of antibiotics based on the current ESCMID guidelines for severe CAP13 (Ampicillin/sulbactam, Amoxicillin/clavulanate, Piperacillin/tazobactam, Ceftriaxone, Cefotaxime, Ceftaroline, Moxifloxacin). The total duration of treatment will be seven days.Τhe dosage, the dosage regime, the route and mode of administration, and the treatment period for the aforementioned antibiotics can be found in the relevant SmPCs (available in References). However, the attending physician may modify the antimicrobial treatment based on risk factors for multidrug-resistance pathogens, microbiology results and local epidemiology. All SoC treatment products and clarithromycin are authorised for use in Greece, where the trial will be conducted.

Drug: Tablets

Clarithromycin

ACTIVE COMPARATOR

These patients will be treated with oral clarithromycin 500 mg twice daily for seven days and it is suggested that all patients receive at least one of antibiotics based on the current ESCMID guidelines for severe CAP13 (Ampicillin/sulbactam, Amoxicillin/clavulanate, Piperacillin/tazobactam, Ceftriaxone, Cefotaxime, Ceftaroline, Moxifloxacin). The total duration of treatment will be seven days.Τhe dosage, the dosage regime, the route and mode of administration, and the treatment period for the aforementioned antibiotics can be found in the relevant SmPCs (available in References). However, the attending physician may modify the antimicrobial treatment based on risk factors for multidrug-resistance pathogens, microbiology results and local epidemiology. All SoC treatment products and clarithromycin are authorised for use in Greece, where the trial will be conducted.

Drug: Clarithromycin 500mg

Interventions

Clarithromycin 500mg DRUG

Oral tablets of 500mg of clarithromycin

Also known as: A β-lactam/β-lactamase inhibitor or a 3rd generation cephalosporin or a fluoroquinolone

Clarithromycin

Tablets DRUG

Oral tablets of similar appearance to active study drug

Also known as: A β-lactam/β-lactamase inhibitor or a 3rd generation cephalosporin or a fluoroquinolone

Placebo

Eligibility Criteria

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

You may qualify if:

• Age equal to or above 18 years
• Male or female gender
• In case of women of reproductive age, willingness to use dual contraceptive method during the study period
• Written informed consent provided by the patient. For subjects without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation
• Community-acquired pneumonia (CAP)
• Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain
• PCT ≥0.25 ng/ml
• suPAR ≥6 ng/ml

You may not qualify if:

• Age below 18 years
• Denial of written informed consent
• Any stage IV malignancy
• Any do not resuscitate decision
• Patients necessitating non-invasive ventilation or mechanical ventilation
• Hospitalization in Intensive Care Unit
• Infection by SARS-CoV-2
• Oral or IV intake of corticosteroids at a daily dose equal to or greater than 0.4 mg/kg prednisone for a period greater than the last 15 days
• Intake of any macrolide for the current episode of CAP under study
• Known infection by the human immunodeficiency virus
• Any chronic anti-cytokine treatment for more than two months
• QTc interval at rest in the ECG ≥500 msec or history of know long QT syndrome
• Medical history of allergy to macrolides
• Concomitant oral intake of astemizole, cizapride, doperidone, pimozide, terfenadine, midazolam, ranolazine, ergot alkaloids (e.g. ergotamine and dihydroergotamine), lomitapide and colchicine; patients may be enrolled in the trial if they stop these drugs during trial participation.
• Medical history of torsades de pointes arrhythmia

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (24)

5th Pulmonary Department, SOTIRIA Athens General Hospital of Chest Diseases

Athens, Athens, 115 27, Greece

RECRUITING

1st Department of Internal Medicine - General Hospital of Athens "Sismanogleio-Amalia Fleming"

Athens, Greece, Greece

NOT YET RECRUITING

1st Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki

Athens, Greece, Greece

RECRUITING

1st Department of Internal Medicine, EVANGELISMOS Athens General Hospital

Athens, Greece, Greece

RECRUITING

1st Department of Internal Medicine, G. GENNIMATAS Athens General Hospital

Athens, Greece, Greece

RECRUITING

1st Department of Internal Medicine, General University Hospital of Ioannina

Athens, Greece, Greece

RECRUITING

1st Department of Internal Medicine, KORGIALENEIO-BENAKEIO E.E.S. Athens General Hospital

Athens, Greece, Greece

RECRUITING

1st Department of Internal Medicine, THRIASIO General Hospital of Elefsis

Athens, Greece, Greece

RECRUITING

1st University Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece, Greece

RECRUITING

2nd Department of Internal Medicine, Attikon University Hospital

Athens, Greece, Greece

RECRUITING

2nd Department of Internal Medicine, THRIASIO General Hospital of Elefsis

Athens, Greece, Greece

RECRUITING

2nd Department of Internal Medicine, TZANEIO Piraeus General Hospital

Athens, Greece, Greece

RECRUITING

2nd Department of Internal Medicine, University General Hospital of Alexandroupolis

Athens, Greece, Greece

RECRUITING

3rd Department of Internal Medicine - General State Hospital of Nikaia "Saint Panteleimon" - West Attica General Hospital

Athens, Greece, Greece

RECRUITING

3rd Department of Internal Medicine, General Hospital of Athens KORGIALENEIO- BENAKEIO E.E.S.

Athens, Greece, Greece

RECRUITING

3rd University Department of Internal Medicine, SOTIRIA Athens General Hospital of Chest Diseases

Athens, Greece, Greece

RECRUITING

4th Department of Internal Medicine, Attikon University Hospital

Athens, Greece, Greece

RECRUITING

6th Pulmonary Medicine Department, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece, Greece

RECRUITING

Department of Chest Medicine, EVANGELISMOS Athens General Hospital

Athens, Greece, Greece

RECRUITING

Department of Internal Medicine, Larissa University General Hospital

Athens, Greece, Greece

RECRUITING

Department of Internal Medicine, Patras University General Hospital

Athens, Greece, Greece

RECRUITING

Department of Pulmonary Medicine, General Hospital of Kerkira

Athens, Greece, Greece

RECRUITING

Emergency Department, TZANEIO Piraeus General Hospital

Athens, Greece, Greece

RECRUITING

3rd Department of Internal Medicine, PAPAGEORGIOU General Hospital of Thessaloniki

Thessaloniki, Thessaloniki, 564 29, Greece

RECRUITING

MeSH Terms

Conditions

Community-Acquired Pneumonia; Sepsis

Interventions

Clarithromycin; Tablets

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Evangelos J Giamarellos-Bourboulis, MD, Phd

  Hellenic Sepsis Study Group

  STUDY CHAIR

Central Study Contacts

Evangelos J Giamarellos-Bourboulis, MD, Phd

CONTACT

2105831994; egiamarel@med.uoa.gr

Athanasia Chatzianastasiou, Phd

CONTACT

6938262747; n.chatzianastasiou@sepsis.gr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, 1:1 randomized, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 5, 2024
• Study Start: February 12, 2024
• Primary Completion: April 5, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (24)