Corona Virus InfectionPhase 4NO COVID-19NCT04316377
Norwegian Coronavirus Disease 2019 Study
A Phase 4 study testing Hydroxychloroquine Sulfate in people with Corona Virus Infection, run by University Hospital, Akershus at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corona Virus Infection
- What is being tested?
- Hydroxychloroquine Sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteNorway
- Study dates
- 25 Mar 2020to 3 Mar 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Requiring ICU admission at screening
- History of psoriasis
- Known adverse reaction to hydroxychloroquine sulphate
- Pregnancy
- Prolonged QT interval (>450 ms)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Corona Virus Infection
- Being tested
- Hydroxychloroquine Sulfate
- Keywords
- Corona virus infection, Chloroquine, Pragmatic trial
- Medical subject headings
- Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine SulfateDrug
Also called Plaquenil
400 mg hydroxychloroquine sulphate (equalling 310 mg base) twice daily for seven days
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Active comparator | Chloroquine therapy in addition to standard of care Receives: Drug: Hydroxychloroquine Sulfate |
| No Treatment | No intervention | Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of decline in SARS-CoV-2 viral load
Viral load assessed by real time polymerase chain reaction in oropharyngeal samples
Measured: Baseline (at randomization) and at 96 hours
Secondary outcomes (13)
Change in National Early Warning Score score
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.
Measured: Baseline (at randomization) and at 96 hours
Admission to intensive care unit
Transfer from regular ward to intensive care unit during index admission
Measured: At all times after randomization during index admission (between admission and discharge, approximately 21 days)
In-hospital mortality
All-cause mortality during index admission
Measured: At all times after randomization during index admission (between admission and discharge, approximately 21 days)
Duration of hospital admission
Total days admitted to the hospital (difference between admission date and discharge date of index admission)
Measured: During index admission (between admission and discharge, approximately 21 days)
Mortality at 30 and 90 days
All-cause mortality assessed at 30 and 90 days
Measured: At follow-up 30 and 90 days
Clinical status
Percentage of subjects reporting each severity rating on a 7-point ordinal scale:
- Death
- Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation
- Hospitalized, on non-invasive ventilation or high flow oxygen devices
- Hospitalized, requiring supplemental oxygen
- Hospitalized, not requiring supplemental oxygen
- Not hospitalized, but unable to resume normal activities
- Not hospitalized, with resumption of normal activities
Measured: 14 days after randomization
Change in C-reactive protein concentrations
Change in C-reactive protein concentrations from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Change in alanine aminotransferase concentrations
Change in alanine aminotransferase concentrations from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Change in aspartate aminotransferase concentrations
Change in aspartate aminotransferase concentrations from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Change in bilirubin concentrations
Change in bilirubin concentrations from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Change in estimated glomerular filtration rate
Change in estimated glomerular filtration rate from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Change in cardiac troponin concentrations
Change in cardiac troponin concentrations from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Change in natriuretic peptide concentrations
Change in natriuretic peptide concentrations from randomization to 96 hours after randomization
Measured: Baseline (at randomization) and at 96 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start25 Mar 2020
- Primary completion25 May 2020
- Study completion3 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Corona Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-arm, open label, pragmatic randomized controlled trial.
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Olav Dalgard, University Hospital, Akershus
- Investigators
- Olav Dalgard, MD PhD, Principal investigator, Akerhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04316377
- Sponsor's protocol ID
- REC 121446
- Acronym
- NO COVID-19
- Status last verified
- Jun 2020
- First submitted
- 13 Mar 2020
- Last updated
- 5 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lyngbakken MN, Berdal JE, Eskesen A, Kvale D, Olsen IC, Rueegg CS, Rangberg A, Jonassen CM, Omland T, Rosjo H, Dalgard O. A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics. Nat Commun. 2020 Oct 20;11(1):5284. doi: 10.1038/s41467-020-19056-6.
PubMed 33082342Lyngbakken MN, Berdal JE, Eskesen A, Kvale D, Olsen IC, Rangberg A, Jonassen CM, Omland T, Rosjo H, Dalgard O. Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 5;21(1):485. doi: 10.1186/s13063-020-04420-0.
PubMed 32503662
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04316377
- Acronym / sponsor ID
- NO COVID-19 / REC 121446
- Conditions
- Corona Virus Infection
- Keywords
- Corona virus infection, Chloroquine, Pragmatic trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University Hospital, AkershusUniversity, hospital or other
- Study start
- 25 Mar 2020 (actual)
- Primary completion
- 25 May 2020 (actual)
- Study completion
- 3 Mar 2025 (estimated)
- First posted
- 20 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two-arm, open label, pragmatic randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Active comparator | Drug: Hydroxychloroquine SulfateChloroquine therapy in addition to standard of care |
| No Treatment | No intervention | –Standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Hospitalised
- Adults 18 year or older
- Moderately severe disease (NEWS score ≤ 6)
- SARS-CoV-2 positive nasopharyngeal swab
- Expected time of admission > 48 hours
Key exclusion criteria (5 listed)
- Requiring ICU admission at screening
- History of psoriasis
- Known adverse reaction to hydroxychloroquine sulphate
- Pregnancy
- Prolonged QT interval (>450 ms)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine SulfateAlso: Plaquenil400 mg hydroxychloroquine sulphate (equalling 310 mg base) twice daily for seven days | Drug | Treatment |
Primary outcome
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
13 secondary outcomes
Change in National Early Warning Score score
Time frame: Baseline (at randomization) and at 96 hours
Admission to intensive care unit
Time frame: At all times after randomization during index admission (between admission and discharge, approximately 21 days)
In-hospital mortality
Time frame: At all times after randomization during index admission (between admission and discharge, approximately 21 days)
Duration of hospital admission
Time frame: During index admission (between admission and discharge, approximately 21 days)
Mortality at 30 and 90 days
Time frame: At follow-up 30 and 90 days
Clinical status
Time frame: 14 days after randomization
Change in C-reactive protein concentrations
Time frame: Baseline (at randomization) and at 96 hours
Change in alanine aminotransferase concentrations
Time frame: Baseline (at randomization) and at 96 hours
Change in aspartate aminotransferase concentrations
Time frame: Baseline (at randomization) and at 96 hours
Change in bilirubin concentrations
Time frame: Baseline (at randomization) and at 96 hours
Change in estimated glomerular filtration rate
Time frame: Baseline (at randomization) and at 96 hours
Change in cardiac troponin concentrations
Time frame: Baseline (at randomization) and at 96 hours
Change in natriuretic peptide concentrations
Time frame: Baseline (at randomization) and at 96 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2020.
- Derived from this study: PubMed 33082342Lyngbakken MN, Berdal JE, Eskesen A, Kvale D, Olsen IC, Rueegg CS, Rangberg A, Jonassen CM, Omland T, Rosjo H, Dalgard O. A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics. Nat Commun. 2020 Oct 20;11(1):5284. doi: 10.1038/s41467-020-19056-6.
- Derived from this study: PubMed 32503662Lyngbakken MN, Berdal JE, Eskesen A, Kvale D, Olsen IC, Rangberg A, Jonassen CM, Omland T, Rosjo H, Dalgard O. Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 5;21(1):485. doi: 10.1186/s13063-020-04420-0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olav Dalgard, MD PhD principal investigator
Akerhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydroxychloroquine Sulfate in people with Corona Virus Infection, run by University Hospital, Akershus at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of decline in SARS-CoV-2 viral load (time frame: Baseline (at randomization) and at 96 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04316377, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2020.