Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial (HOPE)

This is an open label clinical study to evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection. The study aims to document possible prevention of pneumonia in patients staying at home and in improving the symptoms of SARS-CoV-2 pneumonia in patients who will be hospitalised.

Study Overview

• Status: Terminated
• Conditions: Pneumonia, Viral; Covid-19
• Intervention / Treatment: Drug: UNIKINON (Chloroquine phosphate) 200mg tablets

Detailed Description

Humanity has been experiencing a new pandemic of the SARS Coronavirus-19 virus (SARS-CoV-2) since December 2019, causing the disease known as COVID-19. As of March 23, 2020, there have been 382,341 documented episodes of infection worldwide, of which 16,567 have died. An important limitation in the treatment of the disease is the absence of drugs with known antiviral activity against SARS-CoV-2. Recent data suggest that chloroquine has sufficient in vitro activity against the SARS-CoV-2 virus by inhibiting virus entry into cells. It has recently been described that hydroxychloroquine significantly reduces the percentage of patients who have positive sputum in the SARS-CoV-2 virus within 6 days. However, the clinical efficacy of the drug has not been described and it has significant side effects, including more than 10% anorexia, headache, blurred vision, diarrhea or vomiting, and myocardiotoxicity. The frequency of adverse effects of chloroquine in combination with the well-known in vitro activity of chloroquine have led to the design of clinical trials around the world to document the benefits of its use. The present study will evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11144
    • Divine Providence Hospital "Pammakaristos"
  • Athens, Greece, 11527
    • Athens General Hospital "Hippokrateio"
  • Athens, Greece, 11527
    • Athens General Hospital of Thoracic Diseases "SOTIRIA", 1st University Pulmonary Clinic
  • Athens, Greece, 11527
    • Athens General Hospital of Thoracic Diseases "SOTIRIA", 3rd University Pathology Clinic
  • Corfu, Greece, 491 00
    • Corfu General Hospital Agia Irini
  • Ioánnina, Greece, 455 00
    • University General Hospital of Ioannina
  • Maroúsi, Greece, 151 26
    • General Hospital of Athens "Sismanoglio"
  • Thessaloníki, Greece, 54636
    • University General Hospital of Thessaloniki AHEPA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 or older
• Both genders
• For women of childbearing age, they should use or be willing to use a double contraceptive method during the study. A urine pregnancy test to exclude pregnancy will be performed prior to study initiation.
• Written consent after information provided by the patient or the legal representative in the event that the patient cannot consent.
• Upper respiratory or lower respiratory tract infection, as in Annexes II and III respectively.
• Positive respiratory secretion test for SARS-CoV-2 virus by molecular techniques or positive blood IgM titers.

Exclusion Criteria:

• Under 18 years of age
• Denial of written consent
• Any patient case where it has been decided not to rejuvenate
• Serum AST values greater than 5 times the upper normal range
• QTc interval in rest electrocardiogram greater than 500msecs
• Pregnancy or lactation. Urgent pregnancy test to exclude pregnancy before inclusion in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UNIKINON (Chloroquine phosphate); Once a patient is considered eligible for the study, they will receive oral chloroquine phosphate. The total duration of treatment will be 7 days. The dosage will be 500mg every 12 hours. It is clarified that any other treatment at the discretion of the therapist is permitted except for the administration of hydroxychloroquine.	Drug: UNIKINON (Chloroquine phosphate) 200mg tablets; Two and a half tablets (500mg) twice daily for seven days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
50% reduction in symptom score for patients with lower respiratory tract infection	Achieving 50% reduction in symptom score for patients with lower respiratory tract infection on day 8 visit from study initiation.	Day 8 visit from study initiation
Lack of progression for patients with upper respiratory tract infection	Lack of progression to lower respiratory tract infection in patients enrolled in the study due to upper respiratory tract infection on day 8 visit from study initiation.	Day 8 visit from study initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the primary endpoint with respective patients not receiving the treatment	Lower respiratory tract infection rating takes place. The symptoms checked are: Cough, Chest pain, Dyspnea, expectoration. For each symptom score is given from 0 to 3 depending on the intensity and they are summed.	Day 14 visit from study initiation
Serious respiratory failure until day 14. This will be compared with respective patients not receiving the treatment.	It is defined as the presence of both of the following: Respiratory quotient (pO2 / FiO2) less than 150; Need for treatment with CPAP or mechanical ventilation	Day 14 visit from study initiation
Frequency of AEs and SAEs	Frequency of AEs and SAEs	Day 14 visit from study initiation

Collaborators and Investigators

• Sponsor: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
• Collaborators: AHEPA University Hospital; Sismanoglio General Hospital; Athens General Hospital Hippokrateio; Athens General Hospital of Thoracic Diseases SOTIRIA; Divine Providence Hospital Pammakaristos; University General Hospital of Ioannina; Corfu General Hospital Agia Irini
• Investigators: Principal Investigator: Helen Sambatakou, MD, Athens General Hospital "Hippokrateio", 2nd department of Pathology; Principal Investigator: Nikolaos Koulouris, MD, Athens General Hospital of Thoracic Diseases "SOTIRIA", 1st University Pulmonary Clinic; Principal Investigator: Garyfallia Poulakou, MD, Athens General Hospital of Thoracic Diseases "SOTIRIA", 3rd University Pathology Clinic; Principal Investigator: Malvina Lada, MD, General Hospital of Athens "Sismanoglio", 2nd Department of Pathology; Principal Investigator: Ioannis Baraboutis, MD, Divine Providence Hospital "Pammakaristos", Pathology Department; Principal Investigator: Symeon Metallidis, MD, University General Hospital of Thessaloniki AHEPA, 1st University Pathology Clinic; Principal Investigator: Haralambos Milionis, MD, University General Hospital of Ioannina, 1st University Pathology Clinic; Principal Investigator: Ilias Papanikolaou, MD, Corfu General Hospital Agia Irini, Pulmonary Clinic

Publications and helpful links

General Publications

• Arabi YM, Murthy S, Webb S. COVID-19: a novel coronavirus and a novel challenge for critical care. Intensive Care Med. 2020 May;46(5):833-836. doi: 10.1007/s00134-020-05955-1. Epub 2020 Mar 3. No abstract available. Erratum In: Intensive Care Med. 2020 Mar 18;:
• Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 May;55(5):105938. doi: 10.1016/j.ijantimicag.2020.105938. Epub 2020 Mar 12.
• Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2020
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Pneumonia; COVID-19; Chloroquine phosphate
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Pneumonia; Pneumonia, Viral; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Filaricides; Antinematodal Agents; Anthelmintics; Chloroquine; Chloroquine diphosphate
• Other Study ID Numbers: UNIKINON-01/HOPE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No