IVIG for Post-COVID Syndrome
(RECOVER-AUTO Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Duke University
Must not be taking: IVIG, High-dose corticosteroids
Disqualifiers: IVIG allergy, IgA deficiency, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, such as high-dose corticosteroids, omalizumab, and anti-TNF-alpha inhibitors, before joining. If you are on immunosuppressants or low-dose steroids, you must be on a stable dose for more than 4 weeks to participate.
What data supports the effectiveness of the drug IVIG for Post-COVID Syndrome?
Research shows that IVIG has been used to treat severe COVID-19 cases, with studies exploring its potential to help with lung injury, immune system overreactions, and severe infections. While its effectiveness for Post-COVID Syndrome specifically isn't clear, its use in severe COVID-19 suggests it might help with related symptoms.12345
Is IVIG generally safe for humans?
How is the treatment IVIG different from other treatments for post-COVID syndrome?
IVIG (Intravenous Immunoglobulin) is unique because it uses antibodies from donated blood to help regulate the immune system, potentially reducing the overactive immune response seen in severe COVID-19 cases. Unlike other treatments, it can neutralize the suppression of an antibody response against COVID-19 and may offer protection against different virus variants.15111213
Eligibility Criteria
This trial is for individuals who have had COVID-19 and are now experiencing autonomic dysfunction symptoms like rapid heartbeat when standing (POTS). Participants must show an abnormal increase in heart rate upon standing, have a specific score on a questionnaire assessing autonomic symptoms (COMPASS-31 > 40), and meet the general criteria listed under NCT########.Inclusion Criteria
See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
COMPASS-31 Score > 40
My heart races and I feel dizzy or faint when I stand up.
Exclusion Criteria
See NCT06305780 for RECOVER-AUTO: Platform Protocol level exclusion criteria which applies to this appendix (or sub-study)
I have received IVIG treatment before.
My veins cannot be used for infusions.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either IVIG or placebo monthly for 9 months to treat autonomic dysfunction symptoms
36 weeks
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 months
Treatment Details
Interventions
- IVIG (Monoclonal Antibodies)
Trial OverviewThe study is testing different treatments for post-COVID complications affecting the nervous system. It includes IVIG (a blood product used to treat immune deficiencies), a placebo version of IVIG, coordinated care involving multiple healthcare providers, and usual care that patients typically receive.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: IVIG Placebo + Usual CareExperimental Treatment2 Interventions
Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
Group II: IVIG Placebo + Coordinated CareExperimental Treatment2 Interventions
Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
Group III: IVIG + Usual CareExperimental Treatment2 Interventions
IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
Group IV: IVIG + Coordinated CareExperimental Treatment2 Interventions
IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
IVIG is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Intravenous Immunoglobulin for:
- Primary immunodeficiency diseases
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Multifocal motor neuropathy
- Kawasaki disease
- Immune thrombocytopenic purpura (ITP)
🇪🇺 Approved in European Union as Intravenous Immunoglobulin for:
- Primary immunodeficiency syndromes
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Multifocal motor neuropathy
- Kawasaki disease
- Immune thrombocytopenic purpura (ITP)
🇨🇦 Approved in Canada as Intravenous Immunoglobulin for:
- Primary immunodeficiency diseases
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Multifocal motor neuropathy
- Kawasaki disease
- Immune thrombocytopenic purpura (ITP)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
All sites listed under NCT06305780Durham, NC
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Who Is Running the Clinical Trial?
Duke UniversityLead Sponsor
Kanecia Obie ZimmermanLead Sponsor
References
Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial. [2022]Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis.
Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study. [2022]Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients.
Efficacy of IVIG (intravenous immunoglobulin) for corona virus disease 2019 (COVID-19): A meta-analysis. [2022]The benefit of IVIG (Intravenous Immunoglobulin) therapy for COVID-19 remains controversial. We performed a meta-analysis to investigate the efficacy of IVIG treatment in patients with COVID-19.
Intravenous immunoglobulin therapy in COVID-19-related encephalopathy. [2021]To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy.
A single center experience of intravenous immunoglobulin treatment in Covid-19. [2022]Intravenous immunoglobulins (IVIg) have been used in management of severe Covid-19. Here in this study, we report our single-center experience regarding IVIg treatment in management of severe Covid-19.
Side effects of high-dose intravenous immunoglobulins. [2019]Intravenous immunoglobulins (IVIgs) are used increasingly as therapy for neuroimmunologic and other autoimmune diseases. With broader use, the number of reported side effects also is growing. Here we review the literature on adverse reactions reported after administration of i.v.Igs. Despite a few recent reports about a high frequency of complications of IVIgs, by and large they can be considered as safe. Mild and self-limited side effects may occur, but severe complications are rare and often associated with other risk factors for these complications. A careful screening for preexisting illnesses and monitoring of some laboratory parameters can minimize the risks of IVIg therapy.
Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. [2021]Intravenous immunoglobulin G (IVIG) is a blood product from polyvalent and polyclonal immunoglobulin G. It covers a broad range of indications as immunomodulator or replacement therapy. In addition, although it is considered a safe therapy, the incidence of adverse reactions reported in the bibliography ranges from 1 % to 81 %. The objective of this study was to assess IVIG use and describe related adverse events in a tertiary care children's hospital.
Safety evaluation of intravenous immunoglobulin in pediatric patients: a retrospective, 1-year observational study. [2022]Intravenous immunoglobulin (IVIG) is a pooled human plasma protein that has shown efficacy in treating a variety of disorders. IVIG is generally well tolerated and has a good safety profile. There are various IVIG products available on the market, which results in differences in efficacy and safety profile. The aim of this study was to assess the safety profile of IVIG use in pediatric patients and its association with other predicted factors.
A Retrospective Observational Study of Adverse Reactions Associated With Intravenous Immunoglobulin Infusion. [2023]Although intravenous immunoglobulin (IVIG) therapy is generally safe and well tolerated, adverse reactions (ARs) do occur. The majority of these ARs are mild and transient. Risk factors for ARs associate with IVIG infusions are not well established. This study investigated possible risk factors influencing the occurrence of IVIG-associated ARs.
Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions. [2022]Intravenous immunoglobulin (IVIG) is increasingly recommended for many diseases apart from primary immunodeficiency diseases (PID). Although effective and safe, adverse reactions may occur. We conducted a 2-year prospective observational study in 117 patients with PID who received regular IVIG replacement therapy at a median dose of 600 mg/kg every 3 to 4 weeks to examine IVIG's adverse effects; 1765 infusions were performed (mean=15/patient) in 75 males and 42 females (aged 3 months to 77 years) in 3 groups: ≤ 9 years (34.2%), 10-19 years (26.5%), and ≥ 20 years (39.3%). Fifty patients had common variable immunodeficiency (CVID), 11 had X-linked agammaglobulinemia (XLA), and 55 had other immune system disorders. The drugs administered were Octagam® (49.1%), Tegeline® (17.3%), Imunoglobulin® (18.6%), Flebogama® (12.9%), Vigam® (1.2%), and Kiovig® (0.4%). Immediate infusion-related adverse reactions occurred in the cases of 38 out 1765 infusions (2.15%, IC95% 1.53%-2.94%), which were classified as mild (81.6%), moderate (10.5%), or severe (7.9%). Time until reaction ranged from 10 to 240 min (mean = 85.7, median = 60). Reaction rates were similar across age groups. The most common reactions were malaise, headache, and abdominal pain. Reported severe events were tightness of the throat and seizure. All symptoms improved with temporary or complete IVIG interruption and symptomatic medications. Sixteen of 38 reactions to infusions occurred in the presence of an acute infection (p=0.09). Tegeline® represented a greater reaction risk factor than Octagam® (p
Cross-Reactivity of Antibodies in Intravenous Immunoglobulin Preparation for Protection against SARS-CoV-2. [2023]Severe cases of COVID-19 continue to put pressure on medical operations by prolonging hospitalization, occupying intensive care beds, and forcing medical personnel to undergo harsh labor. The eradication of SARS-CoV-2 through vaccine development has yet to be achieved, mainly due to the appearance of multiple mutant-incorporating strains. The present study explored the utility of human intravenous immunoglobulin (IVIG) preparations in suppressing the aggravation of any COVID-19 infection using a SARS-CoV-2 pseudovirus assay. Our study revealed the existence of IgG antibodies in human IVIG preparations, which recognized the spike protein of SARS-CoV-2. Remarkably, the pretreatment of ACE2/TMPRSS2-expressing host cells (HEK293T cells) with IVIG preparations (10 mg/mL) inhibited approximately 40% entry of SARS-CoV-2 pseudovirus even at extremely low concentrations of IgG (0.16-1.25 mg/mL). In contrast, the antibody-dependent enhancement of viral entry was confirmed when SARS-CoV-2 pseudovirus was treated with some products at an IgG concentration of 10 mg/mL. Our data suggest that IVIG may contribute to therapy for COVID-19, including for cases caused by SARS-CoV-2 variants, since IVIG binds not only to the spike proteins of the virus, but also to human ACE2/TMPRSS2. An even better preventive effect can be expected with blood collected after the start of the COVID-19 pandemic.
Treatment of a case of COVID-19 by intravenous immunoglobulin. [2022]Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. As of today, no specific treatment has been found COVID-19. İntravenous immunoglobulin (IVIG) is a widely used therapy to prevent life-threatening infections in patients with primary and secondary immune deficiencies and autoimmune/inflammatory conditions. IVIG administration could be beneficial in the treatment of patients with severe COVID-19. In this respect, this presentation aimed to report a case of COVID-19 treated with IVIG.
How IvIg Can Mitigate Covid-19 Disease: A Symmetrical Immune Network Model. [2022]In this report we provide a hypothesis of how intravenous immunoglobulin (IvIg) (pooled therapeutic normal IgG) mitigates the severe disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The disease is caused by an overreaction of the innate immune system producing a cytokine storm and inflicting multiple organ damage. Our interpretation of IvIg therapy hinges on a recent analysis of the immune dysregulation in Covid-19 infection. Previous infections with common cold coronavirus induce suppressor memory B cells that inhibit an immune response to Covid-19. The repertoire of natural antibodies (IvIg) contains suppressing antibodies in a symmetrically balanced network structure. When this repertoire interacts with the imbalanced network in the infected patient, it can neutralize the suppression of an antibody response against Covid-19. The described scenario for IvIg in Covid-19 infection may also apply in the therapy of autoimmune diseases.