Clinical trial NCT04344951: Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial
Official title: Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pneumonia, Viral
Covid-19
Keywords: COVID-19
Pneumonia
Chloroquine phosphate
SARS-CoV-2
Lead sponsor: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
Sponsor class: INDUSTRY
Collaborators: name: Athens General Hospital Hippokrateio
name: Sotiria Thoracic Diseases Hospital of Athens
name: Sismanoglio General Hospital
name: Divine Providence Hospital Pammakaristos
name: AHEPA University Hospital
name: University Hospital, Ioannina
name: Corfu General Hospital Agia Irini
First posted: 2020-04-14
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, open label, Phase II study
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 50% reduction in symptom score for patients with lower respiratory tract infection
timeFrame: Day 8 visit from study initiation
measure: Lack of progression for patients with upper respiratory tract infection
timeFrame: Day 8 visit from study initiation
Secondary outcomes:
measure: Comparison of the primary endpoint with respective patients not receiving the treatment
timeFrame: Day 14 visit from study initiation
measure: Serious respiratory failure until day 14. This will be compared with respective patients not receiving the treatment.
timeFrame: Day 14 visit from study initiation
measure: Frequency of AEs and SAEs
timeFrame: Day 14 visit from study initiation
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Divine Providence Hospital "Pammakaristos"
city: Athens
country: Greece
facility: Athens General Hospital "Hippokrateio"
city: Athens
country: Greece
facility: Athens General Hospital of Thoracic Diseases "SOTIRIA", 1st University Pulmonary Clinic
city: Athens
country: Greece
facility: Athens General Hospital of Thoracic Diseases "SOTIRIA", 3rd University Pathology Clinic
city: Corfu
country: Greece
facility: Corfu General Hospital Agia Irini
city: Ioánnina
country: Greece
facility: University General Hospital of Ioannina
city: Maroúsi
country: Greece
facility: General Hospital of Athens "Sismanoglio"
city: Thessaloníki
country: Greece
facility: University General Hospital of Thessaloniki AHEPA
Study officials:
affiliation: Athens General Hospital "Hippokrateio", 2nd department of Pathology
name: Helen Sambatakou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Athens General Hospital of Thoracic Diseases "SOTIRIA", 1st University Pulmonary Clinic
name: Nikolaos Koulouris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Athens General Hospital of Thoracic Diseases "SOTIRIA", 3rd University Pathology Clinic
name: Garyfallia Poulakou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital of Athens "Sismanoglio", 2nd Department of Pathology
name: Malvina Lada, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Divine Providence Hospital "Pammakaristos", Pathology Department
name: Ioannis Baraboutis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University General Hospital of Thessaloniki AHEPA, 1st University Pathology Clinic
name: Symeon Metallidis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University General Hospital of Ioannina, 1st University Pathology Clinic
name: Haralambos Milionis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Corfu General Hospital Agia Irini, Pulmonary Clinic
name: Ilias Papanikolaou, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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. RETRACTED: 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.