Ignite Creation Date:
2025-12-25 @ 1:16 AM
Ignite Modification Date:
2025-12-25 @ 11:25 PM
Study NCT ID:
NCT06305793
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-07-23
First Post:
2024-03-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000094024', 'term': 'Post-Acute COVID-19 Syndrome'}, {'id': 'D000086382', 'term': 'COVID-19'}], 'ancestors': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D000094025', 'term': 'Post-Infectious Disorders'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D016756', 'term': 'Immunoglobulins, Intravenous'}], 'ancestors': [{'id': 'D007074', 'term': 'Immunoglobulin G'}, {'id': 'D007132', 'term': 'Immunoglobulin Isotypes'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2024-01-15', 'size': 735901, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_000.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-07-11T10:48', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': 'Double blind'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 200}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2024-03-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2026-07-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-18', 'studyFirstSubmitDate': '2024-03-04', 'studyFirstSubmitQcDate': '2024-03-08', 'lastUpdatePostDateStruct': {'date': '2025-07-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-03-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-04-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Changes in Autonomic Function Testing', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': '* Head-up tilt (HUT) test\n* Valsalva maneuver with a pressure of 40 mmHg for 15 seconds\n* Deep breathing test\n* Skin biopsy (if applicable as per Appendix)\n* Transcranial doppler (TCD), if available'}, {'measure': 'Change in Vanderbilt Orthostatic Symptoms Score (VOSS)', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'The VOSS consists of 9 orthostatic symptoms rated on a scale of 0 (no symptom) to 10 (worst the participant has experienced) at the end of each Head-up Tilt test. Scores range from 0-90 with higher scores representing worse symptoms.'}, {'measure': 'Change in PASC Symptom Questionnaire', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'Participants will be asked to complete a questionnaire that asks about the presence of PASC symptoms. This questionnaire includes additional PASC symptoms that are not directly related to autonomic dysfunction.'}], 'primaryOutcomes': [{'measure': 'Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': '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.'}, {'measure': 'Change in Malmo POTS Symptom Score', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': "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."}, {'measure': 'Change in Active Stand Test', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': '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'}, {'measure': 'Change in blood pressure', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'measured during Active Stand Test'}, {'measure': 'Change in heart rate (HR)', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'measured during Active Stand Test'}, {'measure': 'Change in 6-min Walk Test', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'Normal walking speed will be measured using a standard 6 minute walk'}, {'measure': 'Change in Patient-Reported Outcomes Measurement Information System (PROMIS-29) + 2 Questionnaire', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': '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.\n\nThe 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.'}, {'measure': 'Change in step count as measured by a wearable device', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'measured by activity tracker'}, {'measure': 'Change in heart rate as measured by a wearable device', 'timeFrame': 'Baseline to End of Intervention (9 months)', 'description': 'measured by activity tracker'}, {'measure': 'Proportion of participants who experience individual (SAEs', 'timeFrame': 'Baseline to Follow-up (12 months)', 'description': 'These will be analyzed in the safety population.'}, {'measure': 'Proportion who experience any one or more ( Serious Adverse Event) SAEs', 'timeFrame': 'Baseline to Follow-up (12 months)', 'description': 'These will be analyzed in the safety population.'}, {'measure': 'Incidence of SAEs leading to discontinuation', 'timeFrame': 'Baseline to Follow-up (12 months)', 'description': 'These will be analyzed in the safety population.'}, {'measure': 'Incidence of Events of Special Interest (ESIs)', 'timeFrame': 'Baseline to Follow-up (12 months)', 'description': 'Each study drug may have a unique list of ESIs'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['PASC', 'POTS'], 'conditions': ['Long COVID', 'Long Coronavirus Disease 2019 (Covid19)', 'Long Covid-19']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://recovercovid.org/', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': '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.\n\nThis 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.', 'detailedDescription': '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.\n\nInterventions 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)\n\nAdditional Appendix A (IVIG Sub-study) Level Inclusion Criteria:\n\n1. 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\n2. COMPASS-31 Score \\> 40\n\nExclusion Criteria:\n\n* See NCT06305780 for RECOVER-AUTO: Platform Protocol level exclusion criteria which applies to this appendix (or sub-study)\n\nAdditional Appendix A (IVIG Sub-study) Level Exclusion Criteria:\n\n1. Current or previous IVIG treatment\n2. Contraindication to intravenous immunoglobulin.\n3. 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\n4. Selective IgA deficiency\n5. Current and recent (within 5 half-lives) use of high-dose corticosteroids (for example for prior solid organ transplant), omalizumab, anti-TNF-alpha inhibitors\n6. 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\n7. Significant thrombotic events after the acute phase of COVID-19 and/or within 6 months of enrollment\n8. Veins that are not viable for infusions\n9. Not willing to adhere to dosing schedule for IVIG infusions for 9 months'}, 'identificationModule': {'nctId': 'NCT06305793', 'briefTitle': 'RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)', 'organization': {'class': 'OTHER', 'fullName': 'Duke University'}, 'officialTitle': 'RECOVER-AUTONOMIC (IVIG): Randomized Trial of the Effect of IVIG Versus Placebo on Long COVID Symptoms', 'orgStudyIdInfo': {'id': 'Pro00112597_A'}, 'secondaryIdInfos': [{'id': 'OTA-21-015G', 'type': 'OTHER', 'domain': 'NIH Grant to RTI; RTI subcontracting with DCRI'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'IVIG + Coordinated Care', 'description': 'IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)', 'interventionNames': ['Drug: IVIG (intravenous immunoglobulin)', 'Behavioral: Coordinated Care']}, {'type': 'EXPERIMENTAL', 'label': 'IVIG Placebo + Coordinated Care', 'description': 'Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)', 'interventionNames': ['Drug: IVIG Placebo', 'Behavioral: Coordinated Care']}, {'type': 'EXPERIMENTAL', 'label': 'IVIG + Usual Care', 'description': 'IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)', 'interventionNames': ['Drug: IVIG (intravenous immunoglobulin)', 'Behavioral: Usual Care']}, {'type': 'EXPERIMENTAL', 'label': 'IVIG Placebo + Usual Care', 'description': 'Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)', 'interventionNames': ['Drug: IVIG Placebo', 'Behavioral: Usual Care']}], 'interventions': [{'name': 'IVIG (intravenous immunoglobulin)', 'type': 'DRUG', 'description': '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).', 'armGroupLabels': ['IVIG + Coordinated Care', 'IVIG + Usual Care']}, {'name': 'IVIG Placebo', 'type': 'DRUG', 'description': 'Normal saline given intravenously will be the control (placebo) product. Blinding IV bag and tubing covers will be used for both IVIG and Placebo.\n\nParticipants will receive placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months).', 'armGroupLabels': ['IVIG Placebo + Coordinated Care', 'IVIG Placebo + Usual Care']}, {'name': 'Coordinated Care', 'type': 'BEHAVIORAL', 'description': '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.', 'armGroupLabels': ['IVIG + Coordinated Care', 'IVIG Placebo + Coordinated Care']}, {'name': 'Usual Care', 'type': 'BEHAVIORAL', 'description': 'Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with IVIG administration.', 'armGroupLabels': ['IVIG + Usual Care', 'IVIG Placebo + Usual Care']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27710', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'All sites listed under NCT06305780', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}], 'overallOfficials': [{'name': 'Christopher Grainger, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Duke Clinical Research Institute'}, {'name': 'Cyndya Shibao, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Vanderbilt University Medical Center'}, {'name': 'Peter Novak, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Harvard'}, {'name': 'Pam Taub, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'University of California, San Diego'}, {'name': 'Tae Chung, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Johns Hopkins University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'The summary of results will be shared on the study website: https://recovercovid.org/'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kanecia Obie Zimmerman', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Pediatrics', 'investigatorFullName': 'Kanecia Obie Zimmerman', 'investigatorAffiliation': 'Duke University'}}}}