An Open-label, Clinical Feasibility Study of the Efficacy of Remdesivir for Long-COVID.

Study Overview
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Brief Summary
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Following an infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV2), one in ten people will experience persisting symptoms, or develop symptoms which can last for months and even years. These symptoms affect people in different ways and have been demonstrated to broadly impact physical, mental, and cognitive health. Currently, there are no treatments available to address the issues that patients experience but anti-viral medications have been suggested as being potentially effective. This study will recruit patients that have a confirmed long COVID diagnosis and participants will undertake a series of tests to determine their symptoms and the impact that their condition has had on their bodily systems. The total duration of each participant's involvement is approximately 8 weeks, and this will involve 11 visits (13 visits if taking part in Exeter) at the closest study location (Derby or Exeter). Initial assessments are conducted over three separate visits and then all participants will be scheduled to receive five consecutive days of a medication that has been identified as having the potential to reduce the impact of Long COVID. Following a period of 28 days, participants will be invited to repeat the same tests that were conducted before receiving the medication so that it can be determined how well the drug has worked. In this study we are specifically collecting information to understand how feasible this medication could be to help patients improve their condition and this will help us to determine how likely this drug is able to be used within the wider Long COVID community. The medication that will be used within this study is an existing anti-viral medication (Remdesivir) and if this is possible, we will use this information to conduct a larger trial to determine how well this drug can be used to reduce the impact of Long COVID in a greater number of patients.

Detailed Description
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Following an infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV2), one in ten people will experience persisting symptoms, or develop symptoms which can last for months and even years. These symptoms affect people in different ways and have been demonstrated to broadly impact physical, mental, and cognitive health. Currently, there are no treatments available to address the issues that patients experience but anti-viral medications have been suggested as being potentially effective. This study will recruit patients that have a confirmed long COVID diagnosis and participants will undertake a series of tests to determine their symptoms and the impact that their condition has had on their bodily systems. The total duration of each participant's involvement is approximately 8 weeks, and this will involve 11 visits (13 visits if taking part in Exeter) at the closest study location (Derby or Exeter). Initial assessments are conducted over three separate visits and then all participants will be scheduled to receive five consecutive days of a medication that has been identified as having the potential to reduce the impact of Long COVID. Following a period of 28 days, participants will be invited to repeat the same tests that were conducted before receiving the medication so that it can be determined how well the drug has worked. In this study we are specifically collecting information to understand how feasible this medication could be to help patients improve their condition and this will help us to determine how likely this drug is able to be used within the wider Long COVID community. The medication that will be used within this study is an existing anti-viral medication (Remdesivir) and if this is possible, we will use this information to conduct a larger trial to determine how well this drug can be used to reduce the impact of Long COVID in a greater number of patients.

Official Title
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An Open-label, Clinical Feasibility Study of the Efficacy of Remdesivir for Long-COVID.

Conditions
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SARS-CoV-2 Infection, COVID-19

Intervention / Treatment
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* Drug: Remdesivir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age at the time of enrolment Previously confirmed SARS-CoV-2 infection via PCR and/or lateral flow test. Confirmed or suspected diagnosis of Long COVID by a Health Care Practitioner according to the *definition provided by the World Health Organisation for persistent symptoms following a confirmed SARS-CoV-2 infection. Evidence of persistent symptom profile and severity consistent with Long COVID. Willing and able to provide informed consent, complete the surveys, and complete all planned clinical assessments, and return for scheduled study visits. Has the use of a smart phone. Evidence of persistent symptom profile relative to pre-COVID-19 status as derived from patient reported outcome measures. WHO define Long COVID as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Exclusion Criteria: Treatment history of Remdesivir, molnupiravir, paxlovid and/or any other COVID-19 anti-viral medication (<6 months). Confirmed compromised immune system/function. Currently engaged or previously engaged in a rehabilitation programme or intervention aimed to improve Long COVID symptom profile and/or functional status (in the last 6 months). Recognised as a 'severe risk' of experiencing post-exertional malaise following engagement in physical tasks. Determined using the De Paul symptom questionnaire. Lack of mental capacity to provide informed consent. Unable to understand verbal English/have a hearing impairment that prevents adequate communication.* Participation in another clinical drugs trial within the last 6 months Currently pregnant, breastfeeding or attempting to get pregnant (i.e., not using effective methods of contraception). Currently taking medications known to have an interaction with Remdesivir (e.g., chloroquine phosphate or hydroxychloroquine) as defined by British National Formulary (BNF) information on the selection, prescribing, dispensing and administration of medicines: https://bnf.nice.org.uk/interactions/remdesivir/ History of adverse reactions to anti-viral medication and intravenous/infusions History of Hepatic or Renal Impairment (eGFR (<30ml/min) and LFTs ALT>x5 ULN). Confirm not currently pregnant. Exeter participants only: No recent/long standing history of CT (within 3 months)/ ongoing radiotherapy treatment. Risks of accumulative burden to be discussed as part of study involvement but it is at the discretion of participants. Note: English Comprehension: Potential participants who are unable to understand verbal English will not be eligible for this study. This is due to the necessity of telephone contact which is a key aspect of this study and the unavailability of validated questionnaires in all local languages. Hearing Impairment: Unfortunately, if the participant has a hearing impairment that prevents adequate communication on the telephone, they will not be able to take part in the study. This will be clearly stated in the participant information sheet.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: One study group will receive remdesivir.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Five days of Remdesivir infusion delivered by IV. | Drug: Remdesivir<br>* To be confirmed.<br>* Other names: Veklury;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the feasibility of the use of Remdesivir in the treatment of patients with Long Covid. | To ascertain screening and recruitment rates (overall and by different recruitment pathways | 53 days | 
| Determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | Retention and dropout rate (due to the treatment and/or trial demands) | 53 days | 
| Determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | Adherence to treatment regime | 53 days | 
| Determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | Completeness of study assessments | 53 days | 
| Determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | Completeness of all data collection activities including baseline and +28 days after treatment | 53 days | 
| Determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | Acceptability of outcome measurements | 53 days | 
| Determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | A willingness to take part in a Randomised Control Trial | 53 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify the most clinically relevant primary outcome for the definitive study | • Quality of life, functional status, symptom burden, physical, cognitive and psychological symptoms | 53 days | 
| To identify the most clinically relevant primary outcome for the definitive study | • Physiological function, physical function, cognitive function, and emotional status and/or capacity. | 4 weeks | 
| To identify the most clinically relevant primary outcome for the definitive study | Biomarker and inflammatory profiles | 53 days | 
| To identify the most clinically relevant primary outcome for the definitive study | • Tolerance to physical stimulus: exercise tolerance and reduced post exertional symptom exacerbation following incremental exercise. | 53 days | 
| To identify the most clinically relevant primary outcome for the definitive study | Continuous daily symptoms and heart rate tracking | 53 days | 
| To identify the most clinically relevant primary outcome for the definitive study | • Exeter patients only: Microvascular function: whole body FDG uptake using PET/CT methods. | 53 days | 
| To determine the clinical safety and tolerance and inform the development of a definitive study | To determine the clinical safety and tolerance parameters of the use of Remdesivir in the treatment of patients with Long Covid. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long COVID, Anti-virals, Remdesivir, Long COVID Symptoms