Amantadine for COVID-19

NCT04894617 | Unknown Phase 3

• 2 other identifiers: 020320212021-001177-22
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Corona virus disease 19 (COVID-19) is a devastating pandemic. By early February 2021, more than 102 million people were infected globally with more than 2.2 million reported deaths. Current treatments are approved for hospitalized patients with severe COVID-19 only. No treatment is approved to prevent progression to severe COVID-19 in the early stages of disease. Previous studies have indicated that amantadine is effective against severe acute respiratory syndrome corona virus 1 (SARS-CoV-1). Trials are needed to determine if this translates to a beneficial effect in patients with COVID-19. We hypothesize that preemptive therapy with amantadine of non-hospitalized high-risk adults with SARS-CoV-2 infection disease will prevent disease progression and hospitalization. Methods and analysis: The study is a randomized, double-blinded, placebo-controlled, single center study with two treatment arms; oral amantadine or placebo. Individuals with confirmed SARS-CoV-2 infection and one of following; i) age ≥ 40 years or ii) ≥ 18 years of age with at least one comorbidity or iii) ≥ 18 years of age with a body mass index (BMI) above 30 will be enrolled in the study. We plan to enroll 121 persons in each arm, with a total of 242 participants. Follow up period is 90 days. The primary outcome is disease severity on day 14 assessed by the 8-point COVID outcome scale proposed by the world health organization. Ethics and dissemination: Approvals by the Ethics Committee and National Competent Authorities will be obtained prior to study initiation. Results will be submitted for publication in a peer-reviewed journal and presented at international conferences. Impact: The results of the study will contribute with important knowledge on the efficacy and safety of oral amantadine in the treatment of non-hospitalized high-risk individuals with SARS-CoV-2 infection.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Clinical status on day 14

  Clinical status on day 14 according to 8 point ordinal scale for clinical improvement. No limitations to activities=1, Limitations to activities=2, Hospitalized no oxygen therapy=3, Oxygen by mask or nasal prongs=4, Non-invasive ventilation or high flow oxygen=5, Intubation and mechanical ventilation=6, Ventilation + additional organ support, ECMO=7, Death=8.

  14 days

Secondary Outcomes (7)

• Mortality

  Day 7, 14, 28 and 90

• Mechanical ventilation

  Day 7, 14, 28 and 90

• Hospitalization

  Day 7, 14, 28 and 90

• Duration of hospitalization

  90 days

• PCR SARS-CoV-2

  Day 7

Study Arms (2)

Amantadine

ACTIVE COMPARATOR

The intervention group will receive a dose at day 1 of amantadine 100 mg followed by 100 mg amantadine after 6 hours. The following 4 consecutive days, study participants will receive a daily dose of 200mg amantadine, 100 mg (1 capsule) morning and 100 mg (1 capsule) evening, yielding 5 days of treatment in total (10 capsules in total).

Drug: Amantadine

Placebo

PLACEBO COMPARATOR

The control group will receive placebo treatment with lactose monohydrate; 1 capsule, followed by 1 capsule after 6 hours on day 1. The following 4 consecutive days, study participants will receive 1 capsule morning and 1 capsule evening, yielding 5 days of treatment in total (10 capsules in total).

Drug: Lactose monohydrate

Interventions

Amantadine DRUG

200 mg Amantadine daily for a total of 5 days.

Amantadine

Lactose monohydrate DRUG

Lactose monohydrate two tablet daily for a total of 5 days.

Placebo

Eligibility Criteria

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

You may qualify if:

• Population at risk of developing severe COVID-19, defined as either:
• Age ≥ 40 years
• Age ≥ 18 years and at least one of the following comorbidities: Chronic heart disease without heart failure or proarrhythmic conditions or ventricular arrythmias, diabetes, chronic lung disease, hypertension, chronic kidney disease estimated glomerula filtration rate (GFR)\<60 ml/minute, BMI
• kg/m2.
• For women of childbearing age (defined as non-sterile premenopausal women):
• Negative pregnancy test and willingness to use contraceptive during the study period (90 days)
• ● Provision of informed consent.

You may not qualify if:

• Current hospitalization
• Allergy to amantadine hydrochloride, rimantadine or inactive ingredients.
• Known history of:
• Untreated narrow-angle glaucoma
• Kidney disease with eGFR \< 35 ml/min
• Heart failure, proarrhythmic conditions, ventricular arrhythmias.
• Seizures
• Parkinson's disease
• Gastric ulcer
• Liver Disease
• Hereditary galactose intolerance, lactose intolerance or glucose/galactose malabsorption
• Current use of:
• Neuroleptics/antipsychotics/ levodopa
• Anticholinergics
• Thiazides

Sponsors & Collaborators

• Copenhagen University Hospital, Hvidovre: lead
• University of Copenhagen: collaborator

Study Sites (1)

Copenhagen University Hospital, Hvidovre

Hvidovre, 2650, Denmark

RECRUITING

Related Publications (24)

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MeSH Terms

Conditions

COVID-19

Interventions

Amantadine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Nina M Weis, PhD

  Copenhagen University Hospital, Hvidovre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mette M Rosenkilde, PhD

CONTACT

rosenkilde@sund.ku.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Unblinded personnel will perform randomization into one of two arms (ratio 1:1). The randomization list will be generated centrally in random blocks. Blinded personnel will not have access to the randomization key. Unblinded staff will deliver sealed envelopes containing treatment allocation to blinded study personnel to use for emergency unblinding. All investigators, outcome assessors, and study participants will be blinded to the treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, double-blinded, placebo-controlled study

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 20, 2021
• Study Start: June 1, 2021
• Primary Completion: January 1, 2022
• Study Completion: April 1, 2022
• Last Updated: October 6, 2021

Record last verified: 2021-09

Locations

DK (1)