Long COVIDPhase 2NCT06305793
RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)
A Phase 2 study testing IVIG (intravenous immunoglobulin) and Coordinated Care in people with Long COVID and Long Coronavirus Disease 2019 (Covid19), run by Kanecia Obie Zimmerman at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Long COVID, Long Coronavirus Disease 2019 (Covid19), Long Covid-19
- What is being tested?
- IVIG (intravenous immunoglobulin) and Coordinated Care
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2024to 22 Jun 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
Who cannot join
- 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:
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
All sites listed under NCT06305780
Durham, North Carolina, 27710
About this study
Official title: RECOVER-AUTONOMIC (IVIG): Randomized Trial of the Effect of IVIG Versus Placebo on Long COVID Symptoms
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.
Read the 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.
- Being tested
- IVIG (intravenous immunoglobulin), IVIG Placebo, Coordinated Care, Usual Care
- Keywords
- PASC, POTS
- Medical subject headings
- Post-Acute COVID-19 Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 PlaceboDrug
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 CareBehavioural
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.
Usual CareBehavioural
Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.
| Study group | Role | What they receive |
|---|---|---|
| IVIG + Coordinated Care | Experimental | IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks) Receives: Drug: IVIG (intravenous immunoglobulin); Behavioral: Coordinated Care |
| IVIG Placebo + Coordinated Care | Experimental | Saline: Same dosage as IVIG; monthly for 9 months (36 weeks) Receives: Drug: IVIG Placebo; Behavioral: Coordinated Care |
| IVIG + Usual Care | Experimental | IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks) Receives: Drug: IVIG (intravenous immunoglobulin); Behavioral: Usual Care |
| IVIG Placebo + Usual Care | Experimental | Saline: Same dosage as IVIG; monthly for 9 months (36 weeks) Receives: Drug: IVIG Placebo; Behavioral: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to End of Intervention (9 months)
Secondary outcomes (13)
Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)
The COMPASS-31 is a patient reported outcome that measures autonomic symptoms across multiple domains commonly seen in patients with PASC. Scores range from 0-100 with higher values representing severe symptoms.
Measured: Baseline to End of Intervention (9 months)
Change in Malmo POTS Symptom Score
The Malmo POTS symptom score assesses symptom burden in postural orthostatic tachycardia syndrome (POTS). It is a self-rating, 12-item score (0-10 per item, total range 0-120) based on patients' own perception of symptoms through visual analogue scale assessment. Higher scores represent more pronounced symptoms.
Measured: Baseline to End of Intervention (9 months)
Change in Active Stand Test
Participants will remain supine for 10 minutes, and data will be acquired at 5 and 10 minutes. Standing test should be performed with HR and BP monitoring at 1, 3, 5 and 10 minutes
Measured: Baseline to End of Intervention (9 months)
Change in blood pressure
measured during Active Stand Test
Measured: Baseline to End of Intervention (9 months)
Change in heart rate (HR)
measured during Active Stand Test
Measured: Baseline to End of Intervention (9 months)
Change in 6-min Walk Test
Normal walking speed will be measured using a standard 6 minute walk
Measured: Baseline to End of Intervention (9 months)
Change in Patient-Reported Outcomes Measurement Information System (PROMIS-29) + 2 Questionnaire
The PROMIS-29 consists of 29 items that assess general domains of health and functioning, including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life.
The PROMIS-29+2 is used to calculate a preference score (PROPr) by the addition of two Cognitive Function Ability items. Scores will be reported as T scores ranging from 0 to 100, with a score of 60 being 1 standard deviation above the mean. Higher scores indicate worse overall health.
Measured: Baseline to End of Intervention (9 months)
Change in step count as measured by a wearable device
measured by activity tracker
Measured: Baseline to End of Intervention (9 months)
Change in heart rate as measured by a wearable device
measured by activity tracker
Measured: Baseline to End of Intervention (9 months)
Proportion of participants who experience individual (SAEs
These will be analyzed in the safety population.
Measured: Baseline to Follow-up (12 months)
Proportion who experience any one or more ( Serious Adverse Event) SAEs
These will be analyzed in the safety population.
Measured: Baseline to Follow-up (12 months)
Incidence of SAEs leading to discontinuation
These will be analyzed in the safety population.
Measured: Baseline to Follow-up (12 months)
Incidence of Events of Special Interest (ESIs)
Each study drug may have a unique list of ESIs
Measured: Baseline to Follow-up (12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start8 May 2024
- Primary completion23 Mar 2026
- Study completion22 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Long COVIDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kanecia Obie Zimmerman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kanecia Obie Zimmerman, Duke University
- Investigators
- Christopher Grainger, MD, Study chair, Duke Clinical Research InstituteCyndya Shibao, MD, Study chair, Vanderbilt University Medical CenterPeter Novak, MD, Study chair, HarvardPam Taub, MD, Study chair, University of California, San DiegoTae Chung, MD, Study chair, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06305793
- Sponsor's protocol ID
- Pro00112597_A
- Other IDs
- OTA-21-015G
- Status last verified
- Jul 2026
- First submitted
- 4 Mar 2024
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The summary of results will be shared on the study website: https://recovercovid.org/
Publications
Fudim M, Novak P, Taub PR, Chung T, Zimmerman KO, Moy OV, Fissler HZ, Wen J, Freeman NLB, O'Brien S, Marti H, Cook D, Low P, Kim DY, Rosenberg Y, Granger CB, Shibao CA. Design and rationale of RECOVER-AUTONOMIC: A randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome. Am Heart J. 2026 Jun;296:107384. doi: 10.1016/j.ahj.2026.107384. Epub 2026 Feb 18.
PubMed 41720282
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RECOVER-AUTONOMIC (IVIG): Randomized Trial of the Effect of IVIG Versus Placebo on Long COVID Symptoms
- ClinicalTrials.gov ID
- NCT06305793
- Acronym / sponsor ID
- Pro00112597_A
- Keywords
- PASC, POTS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Kanecia Obie ZimmermanUniversity, hospital or other
- Study start
- 8 May 2024 (actual)
- Primary completion
- 23 Mar 2026 (actual)
- Study completion
- 22 Jun 2026 (actual)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| IVIG + Coordinated Care | Experimental | Drug: IVIG (intravenous immunoglobulin), Behavioral: Coordinated CareIVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks) |
| IVIG Placebo + Coordinated Care | Experimental | Drug: IVIG Placebo, Behavioral: Coordinated CareSaline: Same dosage as IVIG; monthly for 9 months (36 weeks) |
| IVIG + Usual Care | Experimental | Drug: IVIG (intravenous immunoglobulin), Behavioral: Usual CareIVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks) |
| IVIG Placebo + Usual Care | Experimental | Drug: IVIG Placebo, Behavioral: Usual CareSaline: Same dosage as IVIG; monthly for 9 months (36 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
- 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
Key exclusion criteria (11 listed)
- See NCT06305780 for RECOVER-AUTO: Platform Protocol level exclusion criteria which applies to this appendix (or sub-study)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Drug | IVIG + Coordinated Care, IVIG + Usual Care |
| IVIG PlaceboNormal 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). | Drug | IVIG Placebo + Coordinated Care, IVIG Placebo + Usual Care |
| Coordinated CareParticipants 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. | Behavioural | IVIG + Coordinated Care, IVIG Placebo + Coordinated Care |
| Usual CareParticipants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration. | Behavioural | IVIG + Usual Care, IVIG Placebo + Usual Care |
Primary outcome
Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score
Time frame: Baseline to End of Intervention (9 months)
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.
13 secondary outcomes
Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)
Time frame: Baseline to End of Intervention (9 months)
Change in Malmo POTS Symptom Score
Time frame: Baseline to End of Intervention (9 months)
Change in Active Stand Test
Time frame: Baseline to End of Intervention (9 months)
Change in blood pressure
Time frame: Baseline to End of Intervention (9 months)
Change in heart rate (HR)
Time frame: Baseline to End of Intervention (9 months)
Change in 6-min Walk Test
Time frame: Baseline to End of Intervention (9 months)
Change in Patient-Reported Outcomes Measurement Information System (PROMIS-29) + 2 Questionnaire
Time frame: Baseline to End of Intervention (9 months)
Change in step count as measured by a wearable device
Time frame: Baseline to End of Intervention (9 months)
Change in heart rate as measured by a wearable device
Time frame: Baseline to End of Intervention (9 months)
Proportion of participants who experience individual (SAEs
Time frame: Baseline to Follow-up (12 months)
Proportion who experience any one or more ( Serious Adverse Event) SAEs
Time frame: Baseline to Follow-up (12 months)
Incidence of SAEs leading to discontinuation
Time frame: Baseline to Follow-up (12 months)
Incidence of Events of Special Interest (ESIs)
Time frame: Baseline to Follow-up (12 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Derived from this study: PubMed 41720282Fudim M, Novak P, Taub PR, Chung T, Zimmerman KO, Moy OV, Fissler HZ, Wen J, Freeman NLB, O'Brien S, Marti H, Cook D, Low P, Kim DY, Rosenberg Y, Granger CB, Shibao CA. Design and rationale of RECOVER-AUTONOMIC: A randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome. Am Heart J. 2026 Jun;296:107384. doi: 10.1016/j.ahj.2026.107384. Epub 2026 Feb 18.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. The summary of results will be shared on the study website: https://recovercovid.org/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Grainger, MD study chair
Duke Clinical Research Institute
Cyndya Shibao, MD study chair
Vanderbilt University Medical Center
Peter Novak, MD study chair
Harvard
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IVIG (intravenous immunoglobulin) and Coordinated Care in people with Long COVID and Long Coronavirus Disease 2019 (Covid19), run by Kanecia Obie Zimmerman at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score (time frame: Baseline to End of Intervention (9 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06305793, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.