Clinical trial NCT04321616: The Efficacy of Different Anti-viral Drugs in COVID 19 Infected Patients
Official title: The (Norwegian) NOR Solidarity Multicenter Trial on the Efficacy of Different Anti-viral Drugs in SARS-CoV-2 Infected Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: SARS-CoV Infection
COVID 19
Acute Respiratory Distress Syndrome ARDS
Keywords: Effect of drugs
Adverse effects of drugs
SARS-CoV clearance
Duration of artificial ventilation
Duration of intensive care stay
Duration of hospital stay
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2020-03-25
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open randomized adaptive controlled trial
Primary purpose: TREATMENT

Brief summary: The (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.


Eligibility criteria: Inclusion Criteria:

1. Adult patients, 18 years and above
2. Confirmed SARS-2-CoV-2 infection by PCR
3. Admitted to the hospital ward or the ICU
4. Subjects (or legally authorized representative) provides written informed consent prior to initiation of the study

Exclusion Criteria:

1. Severe co-morbidity with life expectancy \<3 months according to investigators assessment
2. (Aspartate Transaminase/ Alanine Aminotransferase) ASAT/ALAT \> 5 times the upper limit of normal
3. Acute co-morbidity within 7 days before inclusion such as myocardial infarction
4. Known intolerance to the available study drugs
5. Pregnancy, possible pregnancy or breast feeding
6. Any reason why, in the opinion of the investigators, the patient should not participate
7. Subject participates in a potentially confounding drug or device trial during the course of the study
8. Prolonged QT interval (\>450 ms)

Primary outcomes:
measure: In-hospital mortality
timeFrame: 3 weeks
Secondary outcomes:
measure: Occurrence and duration of mechanical ventilation
timeFrame: 3 weeks
measure: Occurrence and duration of intensive care unit (ICU) treatment
timeFrame: 3 weeks
measure: Duration of hospital admittance
timeFrame: 1 month
measure: 28 Day mortality
timeFrame: 3 weeks
measure: Viral clearance as assessed by SARS-CoV-2 PCR in peripheral blood and nasopharyngeal airway speciemen
timeFrame: 3 weeks
measure: Occurrence of co-infections
timeFrame: 3 weeks
measure: Occurrence of organ dysfunction
timeFrame: 3 months
Other outcomes:
measure: Inflammatory and anti-inflammatory mediators as assessed in serum and plasma
timeFrame: Throughout hospitalization
measure: Markers of extracellular matrix remodeling
timeFrame: Throughout hospitalization and 3 months after remission
measure: Markers of endothelial activation
timeFrame: Throughout hospitalization
measure: Markers of platelet activation
timeFrame: Throughout hospitalization
Locations:
city: Oslo
country: Norway
facility: Andreas Barratt-Due
Study officials:
affiliation: Oslo University Hospital
name: Paul Aukrust, MD, Professor
role: STUDY_CHAIR
affiliation: Oslo University Hospital
name: Andreas Barratt-Due, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Trine Kåsine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo Hospital Pharmacies
name: Katerina Nezvalova-Henriksen, Pharm D, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Anne Margarita Dyrhol Riise, MD, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Marius Trøseid, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NorCRIN
name: Inge Christoffer Olsen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.
citation: Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, Kasine T, Lund-Johansen F, Hoel H, Holten AR, Tveita A, Mathiessen A, Haugli M, Eiken R, Kildal AB, Berg A, Johannessen A, Heggelund L, Dahl TB, Skara KH, Mielnik P, Le LAK, Thoresen L, Ernst G, Hoff DAL, Skudal H, Kittang BR, Olsen RB, Tholin B, Ystrom CM, Skei NV, Tran T, Dudman S, Andersen JT, Hannula R, Dalgard O, Finbraten AK, Tonby K, Blomberg B, Aballi S, Fladeby C, Steffensen A, Muller F, Dyrhol-Riise AM, Troseid M, Aukrust P; NOR-Solidarity trial. Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Ann Intern Med. 2021 Sep;174(9):1261-1269. doi: 10.7326/M21-0653. Epub 2021 Jul 13.