Long Coronavirus Disease 2019 (Covid19), Long COVID, Long Covid-19
Conditions
Keywords
PASC, POTS
Brief summary
This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating various interventions for use in the treatment of autonomic dysfunction symptoms, including cardiovascular complications and postural orthostatic tachycardia syndrome (POTS), in Post-Acute Sequelae of SARS-CoV-2 infection (PASC) participants. The interventions tested will include non-pharmacologic care and pharmacologic therapies with study drugs.
Detailed description
The hypothesis is that some of the autonomic dysfunction symptoms are immune-mediated, so immunotherapy and other applicable therapies will result in improvement in autonomic symptoms. Interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix.
Interventions
Participants will receive IVIG for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months).
DRUGIVIG Placebo
Normal saline given intravenously will be the control (placebo) product. Blinding IV bag and tubing covers will be used for both IVIG and Placebo. Participants will receive placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months).
BEHAVIORALCoordinated Care
Participants will receive coordinated non-pharmacologic care for a duration of 3 months, concurrent with IVIG administration. Coordinated non-pharmacologic care involves volume expansion through high salt diet, water intake, abdominal binder, exercise/rehabilitation, motivation, education, and assisted care through care coordinator.
BEHAVIORALUsual Care
Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.
Sponsors
Kanecia Obie Zimmerman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind
Intervention model description
In each Appendix trial, each participant will be assigned with equal probability to one of the factorial combinations based on two factors: (1) a study intervention/control and (2) non-pharmacologic intervention/control if the participant is eligible for the study intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study) Additional Appendix A (IVIG Sub-study) Level Inclusion Criteria: 1. Abnormal active standing test defined as presence of orthostatic tachycardia (an increase of 30 beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic hypotension) and experiencing orthostatic symptoms 2. COMPASS-31 Score \> 40
Exclusion criteria
* See NCT06305780 for RECOVER-AUTO: Platform Protocol level
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score | Baseline to End of Intervention (9 months) | The OHQ / OIQ is a measure of orthostatic intolerance and includes a 6-item symptom assessment (OHSA) and the 4-item Daily Activity Scale (OHDAS). Each item is scored from 0 (none/no interference) to 10 (worst possible/complete interference), describing the preceding week. The OHSA composite score is the average of the first 6 non-zero items and the OHDAS composite score is the average of the last 4 non-zero items. The OHQ/OIQ composite score is the average of the OHSA and OHDAS composite scores. The OHQ/OIQ scales at post-baseline are calculated using only those items that were included in the baseline scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Composite Autonomic Symptoms Score 31 (COMPASS-31) | Baseline to End of Intervention (9 months) | The COMPASS-31 is a patient reported outcome that measures autonomic symptoms across multiple domains commonly seen in patients with PASC. Scores range from 0-100 with higher values representing severe symptoms. |
| Change in Malmo POTS Symptom Score | Baseline to End of Intervention (9 months) | The Malmo POTS symptom score assesses symptom burden in postural orthostatic tachycardia syndrome (POTS). It is a self-rating, 12-item score (0-10 per item, total range 0-120) based on patients' own perception of symptoms through visual analogue scale assessment. Higher scores represent more pronounced symptoms. |
| Change in Active Stand Test | Baseline to End of Intervention (9 months) | Participants will remain supine for 10 minutes, and data will be acquired at 5 and 10 minutes. Standing test should be performed with HR and BP monitoring at 1, 3, 5 and 10 minutes |
| Change in blood pressure | Baseline to End of Intervention (9 months) | measured during Active Stand Test |
| Change in heart rate (HR) | Baseline to End of Intervention (9 months) | measured during Active Stand Test |
| Change in 6-min Walk Test | Baseline to End of Intervention (9 months) | Normal walking speed will be measured using a standard 6 minute walk |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS-29) + 2 Questionnaire | Baseline to End of Intervention (9 months) | The PROMIS-29 consists of 29 items that assess general domains of health and functioning, including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life. The PROMIS-29+2 is used to calculate a preference score (PROPr) by the addition of two Cognitive Function Ability items. Scores will be reported as T scores ranging from 0 to 100, with a score of 60 being 1 standard deviation above the mean. Higher scores indicate worse overall health. |
| Change in step count as measured by a wearable device | Baseline to End of Intervention (9 months) | measured by activity tracker |
| Change in heart rate as measured by a wearable device | Baseline to End of Intervention (9 months) | measured by activity tracker |
| Proportion of participants who experience individual (SAEs | Baseline to Follow-up (12 months) | These will be analyzed in the safety population. |
| Proportion who experience any one or more ( Serious Adverse Event) SAEs | Baseline to Follow-up (12 months) | These will be analyzed in the safety population. |
| Incidence of SAEs leading to discontinuation | Baseline to Follow-up (12 months) | These will be analyzed in the safety population. |
| Incidence of Events of Special Interest (ESIs) | Baseline to Follow-up (12 months) | Each study drug may have a unique list of ESIs |
Countries
United States
Contacts
STUDY_CHAIRChristopher Grainger, MD
Duke Clinical Research Institute
STUDY_CHAIRCyndya Shibao, MD
Vanderbilt University Medical Center
STUDY_CHAIRPeter Novak, MD
Harvard
STUDY_CHAIRPam Taub, MD
University of California, San Diego
STUDY_CHAIRTae Chung, MD
Johns Hopkins University
Outcome results
None listed