The researchers propose to develop a Canada-wide, adaptive randomized clinical platform trial to assess the effectiveness of various interventions in patients with lingering symptoms of COVID-19 ("Long COVID"). Participants will be randomized initially to 1 of 3 arms, including placebo (control) and 2 interventions. Because this is an adaptive trial, arms can be dropped if found to be ineffective and new arms can be added. Interventions will last for 2 months and participants will be followed for an additional 4 months (6 months total). Approximately 800-1000 patients with Long COVID will be recruited across Canada. Results from this trial will accelerate the availability of high-quality, real-time evidence and solutions to enable Canada to improve the clinical care of patients with Long COVID.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
460
10mg pills, 2 pills twice per day
400mg pill 3 times per day
Placebo matching ibudilast, 2 pills twice per day OR placebo matching pentoxifylline 1 pill 3 time per day.
The Ottawa Hospital
Ottawa, Ontario, Canada
University Health Network, Osteoporosis Department
Toronto, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
SF-36 physical component score (PCS)
mean change in the SF-36 (v.1) physical component score (PCS)
Time frame: from baseline to two months
Symptoms scale
Three point Likert scale assessing how bothersome symptoms are on a weekly basis for two months then monthly until end of study, as reported by the participant: to provide a granular, detailed picture of the symptom trajectory.
Time frame: Baseline/Randomization weekly to 2 months, then once monthly to 6 months.
Symptom Checklist
Symptom Checklist (adapted from the De Paul Symptom Questionnaire (DSQ2), the World Health Organization Global COVID-19 Clinical Platform's Post COVID-19 CRF and the Symptom Burden Questionnaire for Long COVID): to track symptom trajectory.
Time frame: Baseline/Randomization weekly to 2 months, then once monthly to 6 months.
Six Minute Walking Test (6MWT) with oximetry
Subjects walk as far as they can in six minutes while receiving maximum encouragement. It is simple to execute, inexpensive, standardized and gives a tangible measure of functional exercise capacity. It has been validated in many different populations. The 6MWT will be conducted according to American Thoracic Society standards.
Time frame: Baseline/Randomization and 2 months
TestMyBrain cognitive testing
TestMyBrain was developed as a tool to collect large, population-based samples for understanding the relationship between cognition, emotion, social functioning, and health. This test battery will take about 20 minutes to complete and will assess: verbal, episodic and working memory, attention, processing speed, basic psychomotor response speed, and cognitive control.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Post COVID19 functional status scale
The post-COVID-19 functional status (PCFS) scale focuses on relevant aspects of daily life during follow-up after the infection. The scale is intended to help users become aware of current functional limitations in COVID-19 patients, whether or not as a result of the specific infection, and to objectively determine this degree of disability. The scale is ordinal, has 6 steps ranging from 0 (no symptoms) to 5 (death), and covers the entire range of functional outcomes by focusing on limitations in usual duties/activities either at home or at work/study, as well as changes in lifestyle. The PCFS demonstrates good construct validity.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Reintegration to Normal Living Index (RNLI)
This short self-administered assessment tool will determine the degree to which participants reintegrate into normal social activities such as recreation, mobility in the community and interaction in family and other relationships. This tool has been validated in community living adults with mobility limitations.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Fatigue Scale
The Fatigue Scale was adapted from the De Paul Symptom Questionnaire (DSQ2)'s 38 questions assessing medical history of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS), comorbidities, medications, impact on quality of life and daily activities, etc.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Brief Fatigue inventory
The self-administered Brief Fatigue Inventory is composed of 9 items evaluated on a 10-point scale, assessing severity of fatigue and impact of fatigue on daily life. It takes approximately 2-3 minutes to complete.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Post-Exertional Malaise
The self-administered DPEMQ is comprised of three sections assessing post-exertional malaise (PEM): (i) onset and triggers of PEM (9 questions), (ii) consequences and symptoms (14 questions), (iii) duration, recovery and pacing (7 questions).
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Mental Health - Post-traumatic Stress Disorder Checklist (PCL-5)
The PCL-5 is a validated, reliable, 20-item self-report measure that assesses the 20 Diagnostic and Statistical Manual 5 (DSM-5) symptoms of Post-Traumatic Stress Disorder (PTSD). It takes approximately 5-10 minutes to complete.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Mental Health - General Anxiety Assessment Form (GAD-7)
The GAD-7 is a valid and efficient tool for screening for generalized anxiety disorder and assessing its severity in clinical practice and research. It is an easy-to-use, self-administered patient questionnaire that can be completed in minutes.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Mental Health - Patient Health Questionnaire (PHQ-9)
The PHQ-9 is a validated, multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. It incorporates Diagnostic and Statistical Manual 1V (DSM-IV) depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. The PHQ-9 is brief and useful in clinical practice. The PHQ-9 is completed by the patient in minutes and is rapidly scored by the clinician. The PHQ-9 can also be administered repeatedly, which can reflect improvement or worsening of depression in response to treatment.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Mental Health Composite score (MCS) of the SF-36
The self-administered SF-36 evaluates eight health concepts: physical functioning, role functioning-physical, bodily pain, general health, vitality, social functioning, role functioning-emotional, and mental health. Previous studies have used this instrument in many different populations and it takes approximately 15 minutes to complete.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Dyspnea
Assessed using the Borg Dyspnea scale. This short assessment tool assesses perceived shortness of breath on exertion using a 10 point scale as assessed by the patient.
Time frame: Baseline/Randomization to 1, 2 months 3 and 6 months
Blood samples
Blood samples will be used in correlative studies using advanced multi-omic and machine learning methods to better understand our results so as to identify phenotypes that will benefit from specific therapies
Time frame: Baseline/Randomization and 2 months
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