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Trial record 1 of 1 for:    NCT04316377
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Norwegian Coronavirus Disease 2019 Study (NO COVID-19)

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: NCT04316377
Recruitment Status : Active, not recruiting
First Posted : March 20, 2020
Last Update Posted : June 5, 2020
Sponsor:
Information provided by (Responsible Party):
Olav Dalgard, University Hospital, Akershus

Tracking Information
First Submitted Date  ICMJE March 13, 2020
First Posted Date  ICMJE March 20, 2020
Last Update Posted Date June 5, 2020
Actual Study Start Date  ICMJE March 25, 2020
Actual Primary Completion Date May 25, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
Rate of decline in SARS-CoV-2 viral load [ Time Frame: Baseline (at randomization) and at 96 hours ]
Viral load assessed by real time polymerase chain reaction in oropharyngeal samples
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
Rate of decline in SARS-CoV-2 viral load [ Time Frame: Baseline (at randomization) and at 96 hours ]
Viral load assessed by real time polymerase chain reaction in nasopharyngeal samples
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2020)
  • Change in National Early Warning Score score [ Time Frame: Baseline (at randomization) and at 96 hours ]
    National Early Warning Score score determines the degree of illness of a patient. Scores range from 0-20, with a higher score representing further removal from normal physiology and a higher risk of morbidity and mortality.
  • Admission to intensive care unit [ Time Frame: At all times after randomization during index admission (between admission and discharge, approximately 21 days) ]
    Transfer from regular ward to intensive care unit during index admission
  • In-hospital mortality [ Time Frame: At all times after randomization during index admission (between admission and discharge, approximately 21 days) ]
    All-cause mortality during index admission
  • Duration of hospital admission [ Time Frame: During index admission (between admission and discharge, approximately 21 days) ]
    Total days admitted to the hospital (difference between admission date and discharge date of index admission)
  • Mortality at 30 and 90 days [ Time Frame: At follow-up 30 and 90 days ]
    All-cause mortality assessed at 30 and 90 days
  • Clinical status [ Time Frame: 14 days after randomization ]
    Percentage of subjects reporting each severity rating on a 7-point ordinal scale:
    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized, but unable to resume normal activities
    7. Not hospitalized, with resumption of normal activities
  • Change in C-reactive protein concentrations [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in C-reactive protein concentrations from randomization to 96 hours after randomization
  • Change in alanine aminotransferase concentrations [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in alanine aminotransferase concentrations from randomization to 96 hours after randomization
  • Change in aspartate aminotransferase concentrations [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in aspartate aminotransferase concentrations from randomization to 96 hours after randomization
  • Change in bilirubin concentrations [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in bilirubin concentrations from randomization to 96 hours after randomization
  • Change in estimated glomerular filtration rate [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in estimated glomerular filtration rate from randomization to 96 hours after randomization
  • Change in cardiac troponin concentrations [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in cardiac troponin concentrations from randomization to 96 hours after randomization
  • Change in natriuretic peptide concentrations [ Time Frame: Baseline (at randomization) and at 96 hours ]
    Change in natriuretic peptide concentrations from randomization to 96 hours after randomization
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
  • Change in National Early Warning Score score [ Time Frame: Baseline (at randomization) and at 96 hours ]
    National Early Warning Score score determines the degree of illness of a patient. Scores range from 0-20, with a higher score representing further removal from normal physiology and a higher risk of morbidity and mortality.
  • Admission to intensive care unit [ Time Frame: At all times after randomization during index admission (between admission and discharge, approximately 21 days) ]
    Transfer from regular ward to intensive care unit during index admission
  • In-hospital mortality [ Time Frame: At all times after randomization during index admission (between admission and discharge, approximately 21 days) ]
    All-cause mortality during index admission
  • Duration of hospital admission [ Time Frame: During index admission (between admission and discharge, approximately 21 days) ]
    Total days admitted to the hospital (difference between admission date and discharge date of index admission)
  • Mortality at 30 and 90 days [ Time Frame: At follow-up 30 and 90 days ]
    All-cause mortality assessed at 30 and 90 days
  • Clinical status [ Time Frame: 14 days after randomization ]
    Percentage of subjects reporting each severity rating on a 6-point ordinal scale:
    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Norwegian Coronavirus Disease 2019 Study
Official Title  ICMJE Norwegian Coronavirus Disease 2019 Study: An Open Labeled Randomized Controlled Pragmatic Trial to Evaluate the Antiviral Effect of Chloroquine in Adult Patients With SARS-CoV-2 Infection
Brief Summary In the current proposal, the investigators aim to investigate the virological and clinical effects of chloroquine treatment in patients with established COVID-19 in need of hospital admission. Patients will be randomized in a 1:1 fashion to standard of care or standard of care with the addition of therapy with chloroquine.
Detailed Description

Chloroquine is one of two therapeutics (in addition to remdesivir) that has demonstrated in vitro inhibitory effects on SARS-CoV-2 and the drug is immediately available from national pharmacies. No delay is accordingly expected in treatment initiation after study commencement. In light of the evidence supporting chloroquine as a promising therapeutic in patients with COVID-19, the expected impact of the current proposal is considerable both in the short- and long-term. If successful, treatment with chloroquine has the potential to be the first evidence based treatment for COVID-19. The drug is affordable and the risk of side effects is low, making it an attractive therapeutic in large proportions of the population on a global scale.

In the current proposal aims to investigate the virological and clinical effects of chloroquine treatment in patients with established SARS-CoV-2 in need of hospital admission. The investigators hypothesize that early treatment with chloroquine in patients with established COVID-19 is safe and will significantly improve prognosis and impact clinical outcomes. More specifically, the investigators hypothesize that early treatment with chloroquine will increase the virological clearance rate of SARS-CoV-2, and lead to more rapid resolve of clinical symptoms, decreased proportion of patients with clinical deterioration and a decreased admission rate to intensive care units and in-hospital mortality. Considering the immediate and worldwide health emergency associated with the SARS-CoV-2 outbreak and the current lack of evidence based medical interventions for this patient group, studies investigating such possible treatment modalities in COVID-19 are direly needed.

The study is a two-arm, open label, pragmatic randomized controlled trial (RCT) designed to assess the virological and clinical effect of chloroquine therapy in patients with established COVID-19. Pragmatic clinical trials are characterized by focus on informing decision-makers on optimal clinical medicine practice and an intent to streamline procedures and data collection in the trial. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), pragmatic clinical trials can include a larger number of patients at a short time duration and at a lower cost. Due to the immediate need for study commencement and the time frame of the current proposal, a pragmatic approach will enable swift initiation of randomization and treatment. Data will be extracted from the data warehouse at Akershus University Hospital for eligible patient identification (i.e. electronic surveillance) and for automatic data extraction to the study specific database. The study will not be able to procure an acceptable placebo treatment and the study will accordingly not be placebo-controlled.

All patients at Akershus University Hospital with suspicion of acute respiratory tract infections are examined with a nasopharyngeal swab, with subsequent microbiological examination, including SARS-CoV-2 specific RT-PCR. Participants will be recruited from the entirety of the inpatients at the participating hospitals. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly, with maximum interval 24 hours, for SARS-CoV-2 positive subjects.

The study aims to include patients by a sequential adaptive approach, where analyses are planned after the inclusion of 51 patients, with subsequent analyses after 101, 151 and 202 completed patients. All patients included in each sequence will be used for the final analyses of the entire study. This approach will enable frequent assessment of all outcome measures.

Data will be collected from the hospital electronic record system, including electronic patient records, laboratory and medical imaging systems, and prescribing systems. The data warehouse at Akershus University Hospital will be utilized for automatic data extraction to the study specific database. All clinical variables will be registered in the study eCRF system, including clinical endpoints and quantitative virological results from serial oropharyngeal specimens.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Two-arm, open label, pragmatic randomized controlled trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Corona Virus Infection
Intervention  ICMJE Drug: Hydroxychloroquine Sulfate
400 mg hydroxychloroquine sulphate (equalling 310 mg base) twice daily for seven days
Other Name: Plaquenil
Study Arms  ICMJE
  • Active Comparator: Treatment
    Chloroquine therapy in addition to standard of care
    Intervention: Drug: Hydroxychloroquine Sulfate
  • No Intervention: No Treatment
    Standard of care
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 3, 2020)
53
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2020)
202
Estimated Study Completion Date  ICMJE March 3, 2025
Actual Primary Completion Date May 25, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Hospitalised
  • Adults 18 year or older
  • Moderately severe disease (NEWS score ≤ 6)
  • SARS-CoV-2 positive nasopharyngeal swab
  • Expected time of admission > 48 hours
  • Signed informed consent must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion Criteria:

  • Requiring ICU admission at screening
  • History of psoriasis
  • Known adverse reaction to hydroxychloroquine sulphate
  • Pregnancy
  • Prolonged QT interval (>450 ms)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04316377
Other Study ID Numbers  ICMJE REC 121446
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Olav Dalgard, University Hospital, Akershus
Study Sponsor  ICMJE University Hospital, Akershus
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Olav Dalgard, MD PhD Akerhus University Hospital
PRS Account University Hospital, Akershus
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP