The Efficacy of Different Anti-viral Drugs in COVID 19 Infected Patients

NCT04321616 | Unknown Phase 2 DMC

• 1 other identifier: 118684
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• In-hospital mortality

  All cause in-hospital mortality

  3 weeks

Secondary Outcomes (7)

• Occurrence and duration of mechanical ventilation

  3 weeks

• Occurrence and duration of intensive care unit (ICU) treatment

  3 weeks

• Duration of hospital admittance

  1 month

• 28 Day mortality

  3 weeks

• Viral clearance as assessed by SARS-CoV-2 PCR in peripheral blood and nasopharyngeal airway speciemen

  3 weeks

Other Outcomes (4)

• Inflammatory and anti-inflammatory mediators as assessed in serum and plasma

  Throughout hospitalization

• Markers of extracellular matrix remodeling

  Throughout hospitalization and 3 months after remission

• Markers of endothelial activation

  Throughout hospitalization

Study Arms (3)

Hydroxychloroquine

ACTIVE COMPARATOR

Drug: Remdesivir; Other: (Standard of Care) SoC

Remdesivir

ACTIVE COMPARATOR

Drug: Hydroxychloroquine; Other: (Standard of Care) SoC

Control group - SoC

ACTIVE COMPARATOR

Drug: Hydroxychloroquine; Drug: Remdesivir

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine will be given orally (in the ICU in gastrointestinal tubes) with 800 mg x 2 loading dose followed by 400 mg x 2 every day for a total of 10 days.

Control group - SoC; Remdesivir

Remdesivir DRUG

Remdesivir will be given intravenously 100 mg daily for the duration of the hospitalization and up to 10 days total course. A loading dose of 200 mg at inclusion will be given.

Control group - SoC; Hydroxychloroquine

(Standard of Care) SoC OTHER

The standard of care will be supplied to all patients not receiving a drug intervention.

Hydroxychloroquine; Remdesivir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Andreas Barratt-Due

Oslo, 0756, Norway

RECRUITING

Related Publications (5)

• Patrick-Brown TDJH, Barratt-Due A, Troseid M, Dyrhol-Riise AM, Nezvalova-Henriksen K, Kasine T, Aukrust P, Olsen IC; NOR Solidarity consortium. The effects of remdesivir on long-term symptoms in patients hospitalised for COVID-19: a pre-specified exploratory analysis. Commun Med (Lond). 2024 Nov 12;4(1):231. doi: 10.1038/s43856-024-00650-4.

  PMID: 39533001 DERIVED

• Grundeis F, Ansems K, Dahms K, Thieme V, Metzendorf MI, Skoetz N, Benstoem C, Mikolajewska A, Griesel M, Fichtner F, Stegemann M. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2023 Jan 25;1(1):CD014962. doi: 10.1002/14651858.CD014962.pub2.

  PMID: 36695483 DERIVED

• Tveita A, Murphy SL, Holter JC, Kildal AB, Michelsen AE, Lerum TV, Kaarbo M, Heggelund L, Holten AR, Finbraten AK, Muller KE, Mathiessen A, Boe S, Fevang B, Granerud BK, Tonby K, Lind A, Dudman SG, Henriksen KN, Muller F, Skjonsberg OH, Troseid M, Barratt-Due A, Dyrhol-Riise AM, Aukrust P, Halvorsen B, Dahl TB, Ueland T; NOR-SOLIDARITY Consortium and the Norwegian SARS-CoV-2 Study Group Investigators. High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19. J Infect Dis. 2022 Dec 13;226(12):2150-2160. doi: 10.1093/infdis/jiac313.

  PMID: 35876699 DERIVED

• 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.

  PMID: 34350582 DERIVED

• 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.

  PMID: 34251903 DERIVED

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19

Interventions

Hydroxychloroquine; remdesivir; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Paul Aukrust, MD, Professor

  Oslo University Hospital

  STUDY CHAIR

• Andreas Barratt-Due, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Trine Kåsine, MD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Katerina Nezvalova-Henriksen, Pharm D, PhD

  Oslo Hospital Pharmacies

  PRINCIPAL INVESTIGATOR

• Anne Margarita Dyrhol Riise, MD, Professor

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Marius Trøseid, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Inge Christoffer Olsen, PhD

  NorCRIN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Aukrust, MD, Professor

CONTACT

0047 46778374; paukrust@ous-hf.no

Andreas Barratt-Due, MD, PhD

CONTACT

0047 98209974; andreas.barrattdue@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, MD, PhD

Model Details: An open randomized adaptive controlled trial

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: March 28, 2020
• Primary Completion: August 1, 2020
• Study Completion: November 1, 2020
• Last Updated: April 14, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The study will end according the requirements to WHO
• Access Criteria: WHO COVID 19 investigators

Locations

NO (1)