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

NCT06305793 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro00112597_AOTA-21-015G
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

PASC; POTS

Outcome Measures

Primary Outcomes (1)

• Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score

  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.

  Baseline to End of Intervention (9 months)

Secondary Outcomes (13)

• Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)

  Baseline to End of Intervention (9 months)

• Change in Malmo POTS Symptom Score

  Baseline to End of Intervention (9 months)

• Change in Active Stand Test

  Baseline to End of Intervention (9 months)

• Change in blood pressure

  Baseline to End of Intervention (9 months)

• Change in heart rate (HR)

  Baseline to End of Intervention (9 months)

Other Outcomes (3)

• Changes in Autonomic Function Testing

  Baseline to End of Intervention (9 months)

• Change in Vanderbilt Orthostatic Symptoms Score (VOSS)

  Baseline to End of Intervention (9 months)

• Change in PASC Symptom Questionnaire

  Baseline to End of Intervention (9 months)

Study Arms (4)

IVIG + Coordinated Care

EXPERIMENTAL

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

Drug: IVIG (intravenous immunoglobulin); Behavioral: Coordinated Care

IVIG Placebo + Coordinated Care

EXPERIMENTAL

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

Drug: IVIG Placebo; Behavioral: Coordinated Care

IVIG + Usual Care

EXPERIMENTAL

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

Drug: IVIG (intravenous immunoglobulin); Behavioral: Usual Care

IVIG Placebo + Usual Care

EXPERIMENTAL

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

Drug: IVIG Placebo; Behavioral: Usual Care

Interventions

IVIG (intravenous immunoglobulin) 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).

IVIG + Coordinated Care; IVIG + Usual Care

IVIG Placebo 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).

IVIG Placebo + Coordinated Care; IVIG Placebo + Usual Care

Coordinated Care 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 + Coordinated Care; IVIG Placebo + Coordinated Care

Usual Care BEHAVIORAL

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

IVIG + Usual Care; IVIG Placebo + Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• COMPASS-31 Score \> 40

You may not qualify if:

• Current or previous IVIG treatment
• Contraindication to intravenous immunoglobulin.
• 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
• Selective IgA deficiency
• Current and recent (within 5 half-lives) use of high-dose corticosteroids (for example for prior solid organ transplant), omalizumab, anti-TNF-alpha inhibitors
• 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
• Significant thrombotic events after the acute phase of COVID-19 and/or within 6 months of enrollment
• Veins that are not viable for infusions
• Not willing to adhere to dosing schedule for IVIG infusions for 9 months

Sponsors & Collaborators

• Kanecia Obie Zimmerman: lead

Study Sites (1)

All sites listed under NCT06305780

Durham, North Carolina, 27710, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christopher Grainger, MD

  Duke Clinical Research Institute

  STUDY CHAIR

• Cyndya Shibao, MD

  Vanderbilt University Medical Center

  STUDY CHAIR

• Peter Novak, MD

  Harvard

  STUDY CHAIR

• Pam Taub, MD

  University of California, San Diego

  STUDY CHAIR

• Tae Chung, MD

  Johns Hopkins University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 12, 2024
• Study Start: March 11, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)