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

Kanecia Obie Zimmerman

Status and phase: Enrolling; Phase 2

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

Treatments: Behavioral: Usual Care; Drug: IVIG Placebo; Drug: IVIG (intravenous immunoglobulin); Behavioral: Coordinated Care

Study type: Interventional

Funder types: Other

Identifiers

NCT06305793

Pro00112597_A

OTA-21-015G (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

200 participants in 4 patient groups

IVIG + Coordinated Care

Experimental group

Description:

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

Treatment:

Behavioral: Coordinated Care

Drug: IVIG (intravenous immunoglobulin)

IVIG Placebo + Coordinated Care

Experimental group

Description:

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

Treatment:

Behavioral: Coordinated Care

Drug: IVIG Placebo

IVIG + Usual Care

Experimental group

Description:

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

Treatment:

Drug: IVIG (intravenous immunoglobulin)

Behavioral: Usual Care

IVIG Placebo + Usual Care

Experimental group

Description:

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

Treatment:

Drug: IVIG Placebo

Behavioral: Usual Care