Actively Recruiting

Phase 3
Age: 18Years +
All Genders
ID06294600

Biomarker-Guided Early Clarithromycin Treatment to Prevent Sepsis Progression in Community-Acquired Pneumonia

Led by Hellenic Institute for the Study of Sepsis · Updated on 2025-12-16

330

Participants Needed

24

Research Sites

16 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating the use of early adjunctive clarithromycin treatment guided by the biomarker suPAR to prevent the progression into sepsis in patients with community-acquired pneumonia (CAP) at risk. This phase 3 randomized clinical trial aims to optimize the clinical benefit shown in a previous trial and to provide evidence that early clarithromycin can improve immune response and prevent severe outcomes in CAP patients. The study is motivated by the need for early intervention before severe sepsis develops, using suPAR levels as an early warning tool. Participants will be randomly assigned to receive either oral clarithromycin 500 mg twice daily for seven days plus standard-of-care antibiotics or a placebo tablet twice daily plus standard-of-care antibiotics. The standard antibiotics follow current guidelines and may be adjusted by the doctor based on individual factors. The study includes a quadruple-blind design to compare these two groups and will be conducted in Greece. Treatment duration for both arms is seven days. During the study, participants will have assessments at multiple time points including respiratory symptom scores, organ failure scores (SOFA), and blood tests for inflammatory markers such as procalcitonin and interleukins. The main outcomes will be measured at day 4, with additional follow-up visits at 8, 14, 28, and 90 days to monitor pneumonia resolution, antibiotic use, survival, and mortality. Safety and immune response will also be tracked throughout the study to evaluate the effects of clarithromycin on CAP and sepsis progression.

CONDITIONS

Brief Title

Clarithromycin Treatment to Prevent Sepsis Progression in CAP (REACT)

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age equal to or above 18 years
  • Male or female gender
  • Women of reproductive age must be willing to use dual contraceptive methods during the study
  • Written informed consent provided by the patient or legally designated representative
  • Diagnosis of community-acquired pneumonia (CAP)
  • Presence of at least two of the following signs: cough, purulent sputum expectoration, dyspnea, or pleuritic chest pain
  • Procalcitonin (PCT) level of 0.25 ng/ml or higher
  • suPAR level of 6 ng/ml or higher
Not Eligible

You will not qualify if you...

  • Age below 18 years
  • Denial of written informed consent
  • Any stage IV malignancy
  • Do not resuscitate decision in place
  • Need for non-invasive or mechanical ventilation
  • Hospitalization in Intensive Care Unit
  • Infection by SARS-CoV-2
  • Use of oral or IV corticosteroids at doses of 0.4 mg/kg prednisone or more for over 15 days
  • Use of any macrolide antibiotics for the current CAP episode
  • Known HIV infection
  • Chronic anti-cytokine treatment for more than two months
  • QTc interval at rest of 500 msec or more, or history of long QT syndrome
  • Allergy to macrolides
  • Concurrent use of certain medications unless stopped during the trial (e.g., astemizole, terfenadine, simvastatin)
  • History of torsades de pointes arrhythmia
  • End-stage liver or kidney failure
  • Severe low potassium or magnesium unless corrected
  • Contraindications for macrolide use
  • Pregnancy or lactation
  • Participation in another interventional trial within the last 30 days

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - 7 days

Participants receive oral clarithromycin 500 mg twice daily or placebo tablets for seven days, alongside standard antibiotics for community-acquired pneumonia as per guidelines.

Daily visits or assessments during treatment period

Follow-up

Duration - Up to 90 days

Participants are monitored for resolution of pneumonia, need for antibiotic escalation, survival, and other health outcomes up to 90 days after treatment.

Follow-up visits at approximately 14, 28, and 90 days

Trial Site Locations

Total: 24 locations

1

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

Athens, Athens, Greece, 115 27

Actively Recruiting

2

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

Athens, Greece, Greece

Not Yet Recruiting

3

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

Athens, Greece, Greece

Actively Recruiting

4

1st Department of Internal Medicine, EVANGELISMOS Athens General Hospital

Athens, Greece, Greece

Actively Recruiting

5

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

Athens, Greece, Greece

Actively Recruiting

6

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

Athens, Greece, Greece

Actively Recruiting

7

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

Athens, Greece, Greece

Actively Recruiting

8

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

Athens, Greece, Greece

Actively Recruiting

9

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

Athens, Greece, Greece

Actively Recruiting

10

2nd Department of Internal Medicine, Attikon University Hospital

Athens, Greece, Greece

Actively Recruiting

11

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

Athens, Greece, Greece

Actively Recruiting

12

2nd Department of Internal Medicine, TZANEIO Piraeus General Hospital

Athens, Greece, Greece

Actively Recruiting

13

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

Athens, Greece, Greece

Actively Recruiting

14

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

Athens, Greece, Greece

Actively Recruiting

15

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

Athens, Greece, Greece

Actively Recruiting

16

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

Athens, Greece, Greece

Actively Recruiting

17

4th Department of Internal Medicine, Attikon University Hospital

Athens, Greece, Greece

Actively Recruiting

18

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

Athens, Greece, Greece

Actively Recruiting

19

Department of Chest Medicine, EVANGELISMOS Athens General Hospital

Athens, Greece, Greece

Actively Recruiting

20

Department of Internal Medicine, Larissa University General Hospital

Athens, Greece, Greece

Actively Recruiting

21

Department of Internal Medicine, Patras University General Hospital

Athens, Greece, Greece

Actively Recruiting

22

Department of Pulmonary Medicine, General Hospital of Kerkira

Athens, Greece, Greece

Actively Recruiting

23

Emergency Department, TZANEIO Piraeus General Hospital

Athens, Greece, Greece

Actively Recruiting

24

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

Thessaloniki, Thessaloniki, Greece, 564 29

Actively Recruiting

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Research Team

E

Evangelos J Giamarellos-Bourboulis, MD, Phd

A

Athanasia Chatzianastasiou, Phd

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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