RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)

Purpose

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.

Conditions

  • Long COVID
  • Long Coronavirus Disease 2019 (Covid19)
  • Long Covid-19

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
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
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Double blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
IVIG + Coordinated Care 		IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
  • Drug: IVIG (intravenous immunoglobulin)
    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).
  • Behavioral: Coordinated 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.
Experimental
IVIG Placebo + Coordinated Care 		Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
  • Drug: IVIG 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).
  • Behavioral: Coordinated 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.
Experimental
IVIG + Usual Care 		IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
  • Drug: IVIG (intravenous immunoglobulin)
    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).
  • Behavioral: Usual Care
    Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.
Experimental
IVIG Placebo + Usual Care 		Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
  • Drug: IVIG 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).
  • Behavioral: Usual Care
    Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.

Recruiting Locations

All sites listed under NCT06305780
Durham, North Carolina 27710

More Details

NCT ID
NCT06305793
Status
Recruiting
Sponsor
Kanecia Obie Zimmerman

Study Contact

Orshi Moy
919-668-8060
recoverresearch@duke.edu

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.