Clinical trial NCT06305793: RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)
Official title: RECOVER-AUTONOMIC (IVIG): Randomized Trial of the Effect of IVIG Versus Placebo on Long COVID Symptoms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Long COVID
Long Coronavirus Disease 2019 (Covid19)
Long Covid-19
Keywords: PASC
POTS
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria which applies to this appendix (or sub-study)

Additional Appendix A (IVIG Sub-study) Level Exclusion Criteria:

1. Current or previous IVIG treatment
2. Contraindication to intravenous immunoglobulin.
3. Known allergic reactions to blood products including IVIG and/or subcutaneous immunoglobulin (SCIG), such as history of clinically relevant hemolysis after IVIG infusion, aseptic meningitis, recurrent severe headache, hypersensitivity, severe generalized or severe local skin reactions
4. Selective IgA deficiency
5. Current and recent (within 5 half-lives) use of high-dose corticosteroids (for example for prior solid organ transplant), omalizumab, anti-TNF-alpha inhibitors
6. Use of immunosuppressants such as Plaquenil, or low-dose steroid (prednisone, no more than 10mg a day) will be excluded unless the participant is on stable (\>4 weeks) dose
7. Significant thrombotic events after the acute phase of COVID-19 and/or within 6 months of enrollment
8. Veins that are not viable for infusions
9. Not willing to adhere to dosing schedule for IVIG infusions for 9 months

Primary outcomes:
measure: Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score
timeFrame: Baseline to End of Intervention (9 months)
Secondary outcomes:
measure: Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in Malmo POTS Symptom Score
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in Active Stand Test
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in blood pressure
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in heart rate (HR)
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in 6-min Walk Test
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS-29) + 2 Questionnaire
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in step count as measured by a wearable device
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in heart rate as measured by a wearable device
timeFrame: Baseline to End of Intervention (9 months)
measure: Proportion of participants who experience individual (SAEs
timeFrame: Baseline to Follow-up (12 months)
measure: Proportion who experience any one or more ( Serious Adverse Event) SAEs
timeFrame: Baseline to Follow-up (12 months)
measure: Incidence of SAEs leading to discontinuation
timeFrame: Baseline to Follow-up (12 months)
measure: Incidence of Events of Special Interest (ESIs)
timeFrame: Baseline to Follow-up (12 months)
Other outcomes:
measure: Changes in Autonomic Function Testing
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in Vanderbilt Orthostatic Symptoms Score (VOSS)
timeFrame: Baseline to End of Intervention (9 months)
measure: Change in PASC Symptom Questionnaire
timeFrame: Baseline to End of Intervention (9 months)
Locations:
city: Durham
country: United States
facility: All sites listed under NCT06305780
state: North Carolina
Study officials:
affiliation: Duke Clinical Research Institute
name: Christopher Grainger, MD
role: STUDY_CHAIR
affiliation: Vanderbilt University Medical Center
name: Cyndya Shibao, MD
role: STUDY_CHAIR
affiliation: Harvard
name: Peter Novak, MD
role: STUDY_CHAIR
affiliation: University of California, San Diego
name: Pam Taub, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Tae Chung, MD
role: STUDY_CHAIR
References: