Long COVIDPhase 2NCT06305806

RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)

A Phase 2 study testing Ivabradine and Coordinated Care in people with Long COVID and Long Covid19, run by Kanecia Obie Zimmerman at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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 Covid19, Long Covid-19
What is being tested?: Ivabradine and Coordinated Care
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 181 participants
Where: 1 siteUnited States
Study dates: 11 Mar 2024to 17 Dec 2025
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 B (Ivabradine Sub-study) Level Inclusion Criteria:
1. Abnormal active standing test defined as presence of orthostatic tachycardia and experiencing orthostatic symptoms. Orthostatic tachycardia defined as: Increase of 30 beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic hypotension (decline of ≥ 20 mmHg of systolic or ≥ 10 mmHg of diastolic blood pressure after 3 minutes of standing) OR History of documented increase of 30 bpm or more from an active stand test or tilt table test without orthostatic hypotension in the past 1 year AND standing HR above 100 bpm at the Screening/Baseline visit active stand test.
Exclusions Criteria:
See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
Additional Appendix B (Ivabradine Sub-study) Level Exclusion Criteria:

Show all 18Show fewer

A person of child-bearing potential who is not taking effective contraception
Use of midodrine, pyridostigmine, fludrocortisone, and guanfacine will be excluded unless participant is on a stable dose (>4 weeks). Participants on stable doses will be allowed to continue the medication throughout the study
Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with heart rate reducing properties
Severe hepatic impairment
Use of drugs known to prolong the QT-interval (e.g., quinidine, disopyramide, bepridil, sotalol, amiodarone, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidineUse of drugs known to prolong the QT-interval (e.g., quinidine, disopyramide, bepridil, sotalol, amiodarone, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine
Concomitant use of digoxin or Paxlovid
Known history of atrial fibrillation or significant cardiac arrhythmia not due to reversible cause
Participants who are pacemaker dependent
Patients with hypokalemia (serum K+<3.5 mEq/L)
Patients taking potassium-depleting diuretics, unless potassium level is normal at the baseline CMP, in which case participants may continue taking it during the study.
A history of congenital or acquired long QT syndrome, with or without torsade de pointes
Patients with high degree AV block such as Type 2 AV block, Mobitz II

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

All sites listed under NCT06305780
Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: RECOVER-AUTONOMIC (Ivabradine): Randomized Trial of the Effect of Ivabradine Versus Placebo on Long COVID Symptoms

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 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.

Conditions: Long COVID, Long Covid19, Long Covid-19
Being tested: Ivabradine, Ivabradine Placebo, Coordinated Care, Usual Care
Keywords: PASC, POTS
Medical subject headings: Post-Acute COVID-19 Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IvabradineDrug
Participants will receive ivabradine for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).
Ivabradine PlaceboDrug
The control (placebo) oral tablets will be similar to the study drug, ivabradine.
The control packaging matches the packaging.
Participants will receive placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).
Coordinated CareBehavioural
Participants will receive coordinated non-pharmacologic care for a duration of 3 months, concurrent with ivabradine 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 ivabradine administration.

Study groups in NCT06305806
Study group	Role	What they receive
Ivabradine + Coordinated Care	Experimental	The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm. The table below provides the dosing of ivabradine based on HR. Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID *Resting HR should be measured 5 minutes after lying down Receives: Drug: Ivabradine; Behavioral: Coordinated Care
Ivabradine Placebo + Coordinated Care	Experimental	Not described Receives: Drug: Ivabradine Placebo; Behavioral: Coordinated Care
Ivabradine + Usual Care	Experimental	The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm. The table below provides the dosing of ivabradine based on HR. Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID *Resting HR should be measured 5 minutes after lying down Receives: Drug: Ivabradine; Behavioral: Usual Care
Ivabradine Placebo + Usual Care	Experimental	Not described Receives: Drug: Ivabradine 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 (3 months)

Secondary outcomes (6)

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 (3 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 (3 months)
Change in heart rate (HR)
measured during Active Stand Test
Measured: Baseline to End of Intervention (3 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 (3 months)
Change in 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 (3 months)
Characterize the safety and tolerability of study intervention for treatment of PASC
Adverse events, including serious adverse events (SAEs) and events of special interest (ESIs). Proportion of participants who experience individual SAEs and the proportion who experience any one or more SAEs. Incidence of SAEs leading to discontinuation. Incidence of ESIs.
Measured: Baseline to Follow-up (6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Mar 202417 Dec 2025

First posted12 Mar 2024
Study start11 Mar 2024
Primary completion13 Oct 2025
Study completion17 Dec 2025

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: 181 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06305806
Sponsor's protocol ID: Pro00112597_B
Other IDs: OTA-21-015G
Status last verified: Feb 2026
First submitted: 4 Mar 2024
Last updated: 20 Feb 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Long COVID trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: RECOVER-AUTONOMIC (Ivabradine): Randomized Trial of the Effect of Ivabradine Versus Placebo on Long COVID Symptoms
ClinicalTrials.gov ID: NCT06305806
Acronym / sponsor ID: Pro00112597_B
Conditions: Long COVID, Long Covid19, Long Covid-19
Keywords: PASC, POTS
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 181 participants (actual)
Lead sponsor: Kanecia Obie ZimmermanUniversity, hospital or other
Study start: 11 Mar 2024 (actual)
Primary completion: 13 Oct 2025 (actual)
Study completion: 17 Dec 2025 (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.

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
Ivabradine + Coordinated Care	Experimental	Drug: Ivabradine, Behavioral: Coordinated CareThe starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm. The table below provides the dosing of ivabradine based on HR. Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID *Resting HR should be measured 5 minutes after lying down
Ivabradine Placebo + Coordinated Care	Experimental	Drug: Ivabradine Placebo, Behavioral: Coordinated Care
Ivabradine + Usual Care	Experimental	Drug: Ivabradine, Behavioral: Usual CareThe starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm. The table below provides the dosing of ivabradine based on HR. Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID *Resting HR should be measured 5 minutes after lying down
Ivabradine Placebo + Usual Care	Experimental	Drug: Ivabradine Placebo, Behavioral: Usual Care

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
1. Abnormal active standing test defined as presence of orthostatic tachycardia and experiencing orthostatic symptoms. Orthostatic tachycardia defined as: Increase of 30 beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic hypotension (decline of ≥ 20 mmHg of systolic or ≥ 10 mmHg of diastolic blood pressure after 3 minutes of standing) OR History of documented increase of 30 bpm or more from an active stand test or tilt table test without orthostatic hypotension in the past 1 year AND standing HR above 100 bpm at the Screening/Baseline visit active stand test.
See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
A person of child-bearing potential who is not taking effective contraception
Use of midodrine, pyridostigmine, fludrocortisone, and guanfacine will be excluded unless participant is on a stable dose (>4 weeks). Participants on stable doses will be allowed to continue the medication throughout the study

Key exclusion criteria (0 listed)

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
IvabradineParticipants will receive ivabradine for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).	Drug	Ivabradine + Coordinated Care, Ivabradine + Usual Care
Ivabradine PlaceboThe control (placebo) oral tablets will be similar to the study drug, ivabradine. The control packaging matches the packaging. Participants will receive placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).	Drug	Ivabradine Placebo + Coordinated Care, Ivabradine Placebo + Usual Care
Coordinated CareParticipants will receive coordinated non-pharmacologic care for a duration of 3 months, concurrent with ivabradine 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	Ivabradine + Coordinated Care, Ivabradine Placebo + Coordinated Care
Usual CareParticipants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.	Behavioural	Ivabradine + Usual Care, Ivabradine Placebo + Usual Care

Primary outcome

Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score
Time frame: Baseline to End of Intervention (3 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.

6 secondary outcomes

Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)
Time frame: Baseline to End of Intervention (3 months)
Change in Malmo POTS Symptom Score
Time frame: Baseline to End of Intervention (3 months)
Change in heart rate (HR)
Time frame: Baseline to End of Intervention (3 months)
Change in 6-min Walk Test
Time frame: Baseline to End of Intervention (3 months)
Change in PROMIS-29 + 2 Questionnaire
Time frame: Baseline to End of Intervention (3 months)
Characterize the safety and tolerability of study intervention for treatment of PASC
Time frame: Baseline to Follow-up (6 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 20 Feb 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 Ivabradine and Coordinated Care in people with Long COVID and Long 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 18 inclusion and 0 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 20 Feb 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 (3 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 NCT06305806, 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 20 Feb 2026.