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Amantadine for COVID-19 (ACT)

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ClinicalTrials.gov Identifier: NCT04894617
Recruitment Status : Not yet recruiting
First Posted : May 20, 2021
Last Update Posted : May 25, 2021
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Nina Weis, Copenhagen University Hospital, Hvidovre

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 ≥ 50 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 113 persons in each arm, with a total of 226 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.


Condition or disease Intervention/treatment Phase
Covid19 Drug: Amantadine Drug: Lactose monohydrate Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 226 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blinded, placebo-controlled study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
Official Title: Amantadine for COVID-19: A Randomized, Placebo Controlled, Double-blinded, Clinical Trial
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Amantadine
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
200 mg Amantadine daily for a total of 5 days.

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




Primary Outcome Measures :
  1. Clinical status on day 14 [ Time Frame: 14 days ]

    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.



Secondary Outcome Measures :
  1. Mortality [ Time Frame: Day 7, 14, 28 and 90 ]
    Mortality rate

  2. Mechanical ventilation [ Time Frame: Day 7, 14, 28 and 90 ]
    Incidence of Mechanical ventilation

  3. Hospitalization [ Time Frame: Day 7, 14, 28 and 90 ]
    Incidence of hospitalization

  4. Duration of hospitalization [ Time Frame: 90 days ]
    Duration of hospitalization

  5. PCR SARS-CoV-2 [ Time Frame: Day 7 ]
    Proportion with negative SARS-CoV-2 oropharyngeal swap

  6. Adverse events [ Time Frame: 90 days ]
    Frequency of adverse events

  7. Severe adverse events [ Time Frame: 90 days ]
    Frequency of severe adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Population at risk of developing severe COVID-19, defined as either:

    • Age ≥ 50 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

      • 30 kg/m2.
  • COVID-19 disease confirmed by the presence of SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR) within 5 days prior to inclusion.
  • 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.

Exclusion Criteria:

  • 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
  • Concurrent malignancy requiring chemotherapy
  • Pregnancy and breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04894617


Contacts
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Contact: Mette M Rosenkilde, PhD rosenkilde@sund.ku.dk

Sponsors and Collaborators
Copenhagen University Hospital, Hvidovre
University of Copenhagen
Investigators
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Principal Investigator: Nina M Weis, PhD Copenhagen University Hospital, Hvidovre
Publications:
DIMITROVA EK. Veklury. Eur Med Agency 2020. https://www.ema.europa.eu/en/medicines/human/EPAR/veklury (accessed February 3, 2021).
Research C for DE and. FDA's approval of Veklury (remdesivir) for the treatment of COVID-19-The Science of Safety and Effectiveness. FDA 2020.
Weekly epidemiological update - 2 February 2021 n.d. https://www.who.int/publications/m/item/weekly-epidemiological-update---2-february-2021 (accessed February 3, 2021)
The European Parliament and the Council of the European Union. General Data Protection Regulation. (2016) n.d.
https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf n.d
Sundhedsministeriet. Lov om klage- og erstatningsadgang inden for sundhedsvæsenet 2017

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Responsible Party: Nina Weis, Professor, Copenhagen University Hospital, Hvidovre
ClinicalTrials.gov Identifier: NCT04894617    
Other Study ID Numbers: 02032021
2021-001177-22 ( EudraCT Number )
First Posted: May 20, 2021    Key Record Dates
Last Update Posted: May 25, 2021
Last Verified: May 2021

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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
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Amantadine
Antiparkinson Agents
Anti-Dyskinesia Agents
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents