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

NCT ID: NCT06305793

Last Updated: 2025-07-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-11
• Study Completion Date: 2026-07-01

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

IVIG + Coordinated Care

IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)

Group Type: EXPERIMENTAL

IVIG (intravenous immunoglobulin)

Intervention Type: DRUG

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).

Coordinated Care

Intervention Type: BEHAVIORAL

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.

IVIG Placebo + Coordinated Care

Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)

Group Type: EXPERIMENTAL

IVIG Placebo

Intervention Type: DRUG

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).

Coordinated Care

Intervention Type: BEHAVIORAL

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.

IVIG + Usual Care

IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)

Group Type: EXPERIMENTAL

IVIG (intravenous immunoglobulin)

Intervention Type: DRUG

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).

Usual Care

Intervention Type: BEHAVIORAL

Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.

IVIG Placebo + Usual Care

Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)

Group Type: EXPERIMENTAL

IVIG Placebo

Intervention Type: DRUG

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).

Usual Care

Intervention Type: BEHAVIORAL

Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

Usual Care

Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kanecia Obie Zimmerman

OTHER

Sponsor Role: lead

Responsible Party

Kanecia Obie Zimmerman

Associate Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Christopher Grainger, MD

Role: STUDY_CHAIR

Duke Clinical Research Institute

Cyndya Shibao, MD

Role: STUDY_CHAIR

Vanderbilt University Medical Center

Peter Novak, MD

Role: STUDY_CHAIR

Harvard

Pam Taub, MD

Role: STUDY_CHAIR

University of California, San Diego

Tae Chung, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

All sites listed under NCT06305780

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://recovercovid.org/

Related Info

Other Identifiers

OTA-21-015G

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00112597_A

Identifier Type: -

Identifier Source: org_study_id