Chloroquine, Hydroxychloroquine or Only Supportive Care in Patients AdmItted With Moderate to Severe COVID-19

• Status: Terminated
• Trial end date: 2020-06-08
• Target enrollment: 0
• Participant gender: All

Summary

Rationale: Currently there are no approved treatments for COVID-19. In the Dutch treatment protocol guideline (SWAB) designated treatment is supportive care with the option to add chloroquine base (CQ) or hydroxychloroquine (HCQ). CQ and HCQ are implemented because of their in vitro activity, results from small animal studies, and anecdotal patient's data. There are no published randomized studies with these medications in patients with disease caused by any coronavirus.

Objective: To evaluate if treatment with only supportive care or addition of one of two anti-COVID_19 agents (chloroquine or hydroxychloroquine) results in less disease progression in patients with moderate to severe COVID-19 who require hospital admission.

Study design: Multicentre, cluster randomized cross-over, open label trial. Hospitals will be randomly allocated to one of 3 treatment arms in sequential periods of one week: chloroquine base versus hydroxychloroquine versus supportive care without any drug presumed active against SARS-COV-2. Patients will be treated based on the date of inclusion.

Study population: Adults aged of 18 years and older with moderate to severe, with a NEWS-2 score ≤ 5, laboratory confirmed COVID-19, who require hospital admission in a ward outside the Medium Care or Intensive Care.

Intervention (if applicable): Depending on the treatment arm, the study subject will receive only supportive care or an addition with one of the two agents active against SARS-CoV-2 (chloroquine or hydroxychloroquine).

Main study parameters/endpoints: Disease progression defined as a NEWS-2 score ≥ 7 within 14 days, or admission to Medium Care or Intensive Care Unit, or death.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: UMC Utrecht
• Collaborator: ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Chloroquine; Chloroquine diphosphate; Hydroxychloroquine

Criteria

Inclusion Criteria:

• - Patients (≥18 years of age) admitted to the hospital with confirmed COVID-19 and not needing admission to MC or ICU

• Patient has moderate to severe COVID-19. This will be defined as patients with NEWS-2 score ≤ 5.

• Willing and able to give written informed consent

Exclusion Criteria:

• - Severe Covid-19 defined as NEWS-2 score >5 or admission to the ICU needing ventilation or pressure support.

• Contra-indications for hydroxychloroquine or chloroquine

• Unable to take oral medication (chloroquine and hydroxychloroquine can be administered through tube feeding which is considered oral administration)

• Identified allergies to 4-aminoquinoline

• Severe diseases of the blood system

• 6-phosphate dehydrogenase deficiency

• History of acute myocardial infarction, unstable angina pectoris, severe arrhythmia (frequent ventricular, ventricular tachycardia, ventricular fibrillation) in recent 6 months; New York Heart Association (NYHA) level III-IV

• Known corrected QT interval (QTc) ≥ 500ms.

• Uncorrected severe hypokalaemia (< 2,5 mmol/l) or uncorrected severe hypomagnesemia (< 0.6 mmol/l)

• Pancreatitis

• Refusal to participate expressed by patient or legally authorized representative if they are present