Efficacy of Amantadine Treatment in COVID-19 Patients (TITAN)

Demonstration of the efficacy of amantadine over placebo in the population of patients with moderate or severe COVID-19 in the initial stage of the disease treated in the hospital

Study Overview

• Status: Terminated
• Conditions: Patients With Moderate or Severe COVID-19
• Intervention / Treatment: Drug: Amantadine

Detailed Description

Use of high-doses of amantadine in hospitalized patients in the early phase of moderate or severe COVID-19, compared to placebo, will shorten the duration of the disease and reduce the risk of death and treatment with invasive mechanical ventilation in Intensive Care Units (ICU).

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Białystok, Poland
    • I Klinika Chorób Płuc i Gruźlicy z Pododdziałem Chemioterapii - Uniwersytecki Szpital Kliniczny w Białymstoku
  • Bolesławiec, Poland
    • Szpital Tymczasowy Zespół Opieki Zdrowotnej
  • Bydgoszcz, Poland
    • Oddział Chorób Płuc i Niewydolności Oddychania z Pododdziałem NWM i Pododdziałem Zaburzeń Oddychania w Czasie Snu, Kujawsko - Pomorskie Centrum Pulmonologii w Bydgoszczy
  • Chrzanów, Poland
    • Oddział Chorób Płuc i Chemioterapii - Szpital Powiatowy w Chrzanowie
  • Katowice, Poland
    • Oddział Pneumonologii Górnośląskie Centrum Medyczne im. prof. Leszka Gieca Śląskiego Uniwersytetu Medycznego w Katowicach
  • Limanowa, Poland
    • Oddział Pulmonologii Szpital Powiatowy w Limanowej Imienia Miłosierdzia Bożego
  • Poznań, Poland
    • Oddział Pulmonologiczny Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
  • Pyrzowice, Poland
    • Szpital Tymczasowy w Pyrzowicach
  • Toruń, Poland
    • Oddział Chorób Płuc; Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu
  • Torzym, Poland
    • Oddział gruźlicy i chorób płuc; Lubuski Szpital Specjalistyczny Pulmonologiczno-Kardiologiczny w Torzymiu Spółka z o.o.
  • Warsaw, Poland
    • Tymczasowy Szpital Narodowy, CSK MSWiA
  • Warszawa, Poland
    • Klinika Alergologii, Chorób Płuc i Chorób Wewnętrznych, Centralny Szpital Kliniczny MSWiA w Warszawie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age of respondents - 18 years and older.
2. Confirmation of SARS-CoV-2 infection by PCR

3. Hospitalized patient with COVID-19, defined according to the following criteria (all of the following criteria must be present):

   1. radiological (X-ray of klp or TK klp) features of pneumonia,
   2. blood saturation (SaO2) measured at rest in the absence of oxygen <95%,
   3. it is not necessary to apply on the day of patient enrollment: high-flow oxygen therapy or mechanical ventilation (non-invasive or invasive).
4. Time up to 10 days from the onset of COVID-19 symptoms. The onset of COVID-19 symptoms is the first day on which the first symptom typical for SARS-CoV-2 or COVID-19 infection (in the opinion of the attending physician at the center) occurred, such as: fever, cough, shortness of breath, changes in taste or smell , muscle pain, chest pain, diarrhea, nausea, vomiting, sore throat, nasal congestion.

Exclusion Criteria:

1. Pregnancy or lactation

2. Presence of medical contraindications for inclusion in the examination in the opinion of the attending physician, in particular:

   a) comorbidities: i) clinically significant hepatic or renal insufficiency; ii) epilepsy or seizures (current or history of); iii) psychiatric or somatic diseases (present or in a history of agitation or confusion, delirium syndromes or exogenous psychoses); iv) cardiovascular diseases such as: severe congestive heart failure, cardiomyopathy, myocarditis, grade II-IV AV block, bradycardia, QT prolongation, perceived U waves or family history of congenital long QT syndrome, severe ventricular arrhythmias a history of heart (including torsade de pointes); v) diseases or conditions that significantly reduce the immunity of a patient (e.g. solid organ transplant, bone marrow transplantation (BMT), AIDS, immune biologics and / or high-dose steroids (> 20 mg prednisone daily).

   b) hypersensitivity to any component of the preparation, c) parallel use of drugs that prolong the QT interval, d) hypokalemia or hypomagnesaemia, e) untreated angle-closure glaucoma, f) use of amantadine currently or in the last 3 months prior to study inclusion; g) participation in another clinical program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Amantadine; Patients are treated with high doses of amantadine.
Experimental: Amantadine	Drug: Amantadine; Patients are treated with high doses of amantadine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recovery	Time to recovery, defined as the first day during the 28-day clinical follow-up during which the patient's clinical condition is graded 1, 2, or 3 on an eight-point "Normal Symptom Score"	28 days

Collaborators and Investigators

• Sponsor: Noblewell
• Collaborators: Medical Research Agency, Poland; Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice, Poland
• Investigators: Study Director: Adam Barczyk, Prof., Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Actual): March 10, 2022
• Study Completion (Actual): March 10, 2022

Study Registration Dates

• First Submitted: June 28, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; SARS-COV-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: 00980.045; 2021-000981-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No