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

NCT04362332 | Terminated Phase 4 DMC

• 1 other identifier: NL73529.041.20 versie 3
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COVID-19

Keywords

chloroquine; hydroxychloroquine; randomized

Outcome Measures

Primary Outcomes (1)

• Composite endpoint with disease progression defined as a NEWS2score ≥ 7 within 14 days or resulting in admission to Intensive/Medium Care unit or resulting in death within 14 days.

  Composite endpoint with disease progression defined as a NEWS2score ≥ 7 within 14 days or resulting in admission to Intensive/Medium Care unit or resulting in death within 14 days.

  14 days

Secondary Outcomes (1)

• Side effects

  28 days

Study Arms (3)

chloroquine

ACTIVE COMPARATOR

1\. Supportive care + chloroquine base arm: loading dose 600mg, followed by 300mg 12 hours later, followed by 300mg bid for 4 days; total treatment duration of 5 days

Drug: Chloroquine Sulfate; Other: Standard supportive care

hydroxychloroquine

ACTIVE COMPARATOR

2\. Supportive care + hydroxychloroquine arm: loading dose 400mg bid, followed by 200mg bid for 4 days; total treatment duration of 5 days.

Drug: Hydroxychloroquine; Other: Standard supportive care

Supportive care only

NO INTERVENTION

3\. Supportive care only.

Interventions

Chloroquine Sulfate DRUG

cluster randomized

chloroquine

Hydroxychloroquine DRUG

cluster randomized

hydroxychloroquine

Standard supportive care OTHER

cluster randomized

chloroquine; hydroxychloroquine

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• \- 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
• 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

Sponsors & Collaborators

• UMC Utrecht: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

UMCU

Utrecht, 3508GA, Netherlands

Location

MeSH Terms

Conditions

COVID-19

Interventions

Chloroquine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: cluster randomized design
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Infectious Diseases

Model Details: 1. Supportive care + chloroquine base arm: loading dose 600mg, followed by 300mg 12 hours later, followed by 300mg bid for 4 days; total treatment duration of 5 days 2. Supportive care + hydroxychloroquine arm: loading dose 400mg bid, followed by 200mg bid for 4 days; total treatment duration of 5 days. 3. Supportive care only.

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 24, 2020
• Study Start: April 14, 2020
• Primary Completion: June 8, 2020
• Study Completion: June 8, 2020
• Last Updated: June 19, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 12 months

Locations

NL (1)