Anti-inflammatory Clarithromycin for Improving COVID-19 Infection Early

NCT04398004 | Completed Phase 2

• 2 other identifiers: ACHIEVE2020-001882-36
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 9

Brief Summary

Recent information appearing from different countries suggest that treatment of Coronavirus disease 2019 (COVID-19) with hydroxychloroquine or with a combination of hydroxychloroquine and azithromycin has either an indifferent effect on viral replication or substantial cardiotoxicity. This is a clinical trial aiming to prove that addition of oral clarithromycin to treatment regimen of COVID-19 is associated with early clinical improvement and attenuation of the high inflammatory burden of the host. The study will not comprise a placebo-comparator group since this is considered inappropriate in an era of a pandemic with substantial global mortality.

Conditions

COVID-19; Virus Diseases; Corona Virus Infection

Keywords

COVID-19; SARS-CoV-2; Clarithromycin; Hydroxychloroquine

Outcome Measures

Primary Outcomes (2)

• Clinical outcome negative for two parameters(hospital admission/disease progression)

  This is defined on day 8 (End of Treatment - EOT). Patients with upper respiratory tract infection by SARS-CoV-2 meet the study primary endpoint if they were not admitted to hospital or their symptoms did not progress to lower respiratory tract infection. Patients who develop by day 8 severe respiratory failure do not meet the study primary endpoint.

  Day 1 to Day 8

• At least 50% change of the score of respiratory symptoms from the baseline

  This is defined on day 8 (EOT visit). Patients with lower respiratory tract infection by SARS-CoV-2 meet the primary endpoint if they present at least 50% decrease of the score of respiratory symptoms from the baseline. This score is the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain. Patients who develop by day 8 severe respiratory failure do not meet the study primary endpoint. Score ranges from 0 (no symptoms) to 9 (worst for all symptoms).

  Day 1 to Day 8

Secondary Outcomes (16)

• Comparison of two parameters with historical comparators from Hellenic Sepsis Study Group Database

  Day 1 to Day 8

• Comparison of the score of respiratory symptoms with historical comparators from Hellenic Sepsis Study Group Database

  Day 1 to Day 8

• Clinical outcome negative for two parameters(hospital admission/disease progression) on day 4

  Day 4

• At least 50% change of the score of respiratory symptoms from the baseline on day 4

  Day 4

• Range of development of severe respiratory failure

  Day 1 to Day 14

Study Arms (1)

Clarithromycin arm

EXPERIMENTAL

Treatment will last for seven days. Every patient will receive one tablet of 500 mg of clarithromycin every 12 hours. It is explicitly stated that all other treatment is allowed with the only exclusion the parallel intake of a) any other drug of the macrolide class of antibiotics; and/or b) hydroxychloroquine or chloroquine phosphate. Drugs contraindicated with the intake of clarithromycin are also not allowed, as they are described in the local label information.

Drug: Clarithromycin

Interventions

Clarithromycin DRUG

Treatment with 500 mg Clarithromycin orally twice daily for seven days

Also known as: Klaricid

Clarithromycin arm

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Male of female gender
• Written informed consent provided by the patients or by a first-degree relative in case of patients unable to consent
• In case of women, unwillingness to remain pregnant during the study period achieved either by their partner using condom or by themselves using oral contraceptives.
• Confirmed infection by SARS-CoV-2 virus
• Infection of the upper respiratory tract or of the lower respiratory tract

You may not qualify if:

• Age below 18 years
• Denial of written informed consent
• Intake of any macrolide for the current episode of infection under study
• Intake of hydroxychloroquine or chloroquine phosphate.
• Presence of severe respiratory failure
• Oral or intravenous intake of corticosteroids defined as any more than 0.4mg/kg daily intake of equivalent prednisone for the last 15 days
• Neutropenia defined as an absolute neutrophil count below 1,000/mm3
• Presence of any contraindications for the study drugs as stated in local label information
• QTc interval at rest electrocardiogram ≥500 msec or history of known congenital long QT syndrome
• Pregnancy or lactation

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (9)

COVID-19 Department, General Hospital of Attica SISMANOGLEIO-AMALIA FLEMING

Marousi, Athens, 15126, Greece

Location

2nd Department of Internal Medicine, General Hospital of Nikaia

Piraeus, Attica, 18454, Greece

Location

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

Alexandroupoli, 68100, Greece

Location

1st University Department of Internal Medicine, LAIKO General Hospital of Athens

Athens, 11527, Greece

Location

2nd University Department of Internal Medicine, IPPOKRATEION General Hospital of Athens

Athens, 11527, Greece

Location

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

Athens, 11527, Greece

Location

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

Ioannina, 45500, Greece

Location

2nd Department of Internal Medicine, General Hospital of Piraeus "Tzaneio"

Piraeus, 18536, Greece

Location

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

Thessaloniki, 54621, Greece

Location

Related Publications (1)

• Tsiakos K, Tsakiris A, Tsibris G, Voutsinas PM, Panagopoulos P, Kosmidou M, Petrakis V, Gravvani A, Gkavogianni T, Klouras E, Katrini K, Koufargyris P, Rapti I, Karageorgos A, Vrentzos E, Damoulari C, Zarkada V, Sidiropoulou C, Artemi S, Ioannidis A, Papapostolou A, Michelakis E, Georgiopoulou M, Myrodia DM, Tsiamalos P, Syrigos K, Chrysos G, Nitsotolis T, Milionis H, Poulakou G, Giamarellos-Bourboulis EJ. Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial. Infect Dis Ther. 2021 Dec;10(4):2333-2351. doi: 10.1007/s40121-021-00505-8. Epub 2021 Aug 6.

  PMID: 34363189 DERIVED

MeSH Terms

Conditions

COVID-19; Virus Diseases; Coronavirus Infections

Interventions

Clarithromycin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Garyfallia Poulakou, MD, PhD

  National Kapodistrian University of Athens, Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment with clarithromycin

Study Record Dates

• First Submitted: May 17, 2020
• First Posted: May 21, 2020
• Study Start: May 6, 2020
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (9)