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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04362332
Recruitment Status : Terminated (Currently, almost no patients admitted to Dutch hospitals. If any effect of HCQ is to be expected we need more than 1000 inclusions)
First Posted : April 24, 2020
Last Update Posted : June 19, 2020
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Andy I.M. Hoepelman, UMC Utrecht

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.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Chloroquine Sulfate Drug: Hydroxychloroquine Other: Standard supportive care Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
  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.
Masking: None (Open Label)
Masking Description: cluster randomized design
Primary Purpose: Treatment
Official Title: An Open Label Cluster Randomized Controlled Trial of Chloroquine, Hydroxychloroquine or Only Supportive Care in Patients AdmItted With Moderate to Severe COVID-19
Actual Study Start Date : April 14, 2020
Actual Primary Completion Date : June 8, 2020
Actual Study Completion Date : June 8, 2020


Arm Intervention/treatment
Active Comparator: chloroquine
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
cluster randomized

Other: Standard supportive care
cluster randomized

Active Comparator: hydroxychloroquine
2. Supportive care + hydroxychloroquine arm: loading dose 400mg bid, followed by 200mg bid for 4 days; total treatment duration of 5 days.
Drug: Hydroxychloroquine
cluster randomized

Other: Standard supportive care
cluster randomized

No Intervention: Supportive care only
3. Supportive care only.



Primary Outcome Measures :
  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. [ Time Frame: 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.


Secondary Outcome Measures :
  1. Side effects [ Time Frame: 28 days ]
    Secondary study parameters/endpoints Side effects of different drugs leading to regimen change or discontinuation of the antiviral treatment



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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04362332


Locations
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Netherlands
UMCU
Utrecht, Netherlands, 3508GA
Sponsors and Collaborators
UMC Utrecht
ZonMw: The Netherlands Organisation for Health Research and Development
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Responsible Party: Andy I.M. Hoepelman, Head of Infectious Diseases, UMC Utrecht
ClinicalTrials.gov Identifier: NCT04362332    
Other Study ID Numbers: NL73529.041.20 versie 3
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: June 19, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 12 months

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Andy I.M. Hoepelman, UMC Utrecht:
chloroquine
hydroxychloroquine
randomized
Additional relevant MeSH terms:
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Hydroxychloroquine
Chloroquine
Chloroquine diphosphate
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Amebicides
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics