Clinical trial NCT04480424: Study to Evaluate the Safety and Efficacy of High Dose Intravenous Immune Globulin (IVIG) Plus Standard Medical Treatment (SMT) Versus SMT Alone in Participants in Intensive Care Unit (ICU) With Coronavirus Disease (COVID-19)
Official title: A Multicenter, Randomized, Open-label Parallel Group Pilot Study to Evaluate Safety and Efficacy of High Dose Intravenous Immune Globulin (IVIG) Plus Standard Medical Treatment (SMT) Versus SMT Alone in Subjects With COVID-19 Requiring Admission to the Intensive Care Unit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus Disease
Severe acute respiratory syndrome coronavirus 2
SARS-CoV-2
Coronavirus Infections
Coronaviridae Infections
Virus Diseases
Immunoglobulins
Antibodies
Gamma-globulins
Immunoglobulins, Intravenous
Immunologic Factors
Physiological Effects of Drugs
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine if a high dose of Intravenous Immune Globulin (IVIG) plus Standard Medical Treatment (SMT) can reduce all-cause mortality versus SMT alone in hospitalized participants with COVID-19 requiring admission to the ICU through Day 29.


Eligibility criteria: Inclusion Criteria:

* Hospitalized male or female subjects of ≥ 18 years of age at time of Screening who are being treated in the ICU for COVID-19 for not longer than 48 hours or for whom a decision has been made that COVID-19 disease severity warrants ICU admission.
* Has laboratory-confirmed novel coronavirus {SARS-CoV-2} infection as determined by qualitative polymerase chain reaction (PCR) (reverse transcriptase \[RT\]-PCR), or other United States Food and Drug Administration (FDA)-approved diagnostic assay for COVID-19 in any specimen during the current hospital admission prior to randomization.
* Illness (symptoms of COVID-19 of any duration requiring ICU level care), and the following:

  1. Radiographic infiltrates by imaging (chest X-Ray, computerized tomography (CT) scan, etc.), and
  2. Requiring mechanical ventilation and/or supplemental oxygen.
* Any one of the following related to COVID-19: i. Ferritin \> 400 nanogram per milliliter (ng/mL), ii. Lactate dehydrogenase (LDH) \> 300 units per liter (U/L), iii. D-Dimers \> reference range, or iv. C-reactive protein (CRP) \> 40 milligram per liter (mg/L).
* Subject provides informed consent prior to initiation of any study procedures.

Exclusion Criteria:

* Clinical evidence of any significant acute or chronic disease or pathophysiologic manifestations (eg, complications of COVID-19 standard medical treatments) that, in the opinion of the investigator, may place the subject at undue medical risk.
* The subject has had a known (documented) serious anaphylactic reaction to blood, any blood-derived or plasma product or a past history of any hypersensitivity reactions to commercial immunoglobulin.
* A medical condition in which the infusion of additional fluid is contraindicated.
* Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered by the Principal Investigator not able to be reversed.
* Subjects with known (documented) thrombotic complications to polyclonal IVIG therapy in the past.
* Subjects with current or prior myocardial infarction, stroke, deep vein thrombosis, or thromboembolic event (within the past 12 months) or who have a history of thromboembolic events of unknown etiology.
* Subjects with limitations of therapeutic effort.
* Female subjects who are pregnant or of child-bearing potential with a positive test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at Screening/Baseline.
* Subjects participating in another interventional clinical trial with investigational medical product or device.
* Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome.
* Presence of malignancy (either new diagnosis of malignancy or known residual disease) within the past 12 months.
* Creatinine at Screening is ≥ 4 mg/dL (or subject is dependent on dialysis/renal replacement therapy).
* Known Immunoglobulin A (IgA) deficiency with anti-IgA serum antibodies.
* Uncontrolled hypertension at the time of Screening (systolic blood pressure \> 200 mm Hg) or refractory severe hypotension with sustained systolic blood pressure \< 90 mm Hg unresponsive to vasopressors.

Primary outcomes:
measure: All-Cause Mortality Rate Through Day 29
timeFrame: Up to Day 29
Secondary outcomes:
measure: Percentage of Participants With Actual Intensive Care Unit (ICU) Discharge Time
timeFrame: Up to Day 29
measure: Duration of Mechanical Ventilation
timeFrame: Up to Day 29
measure: Percentage of Participants With Actual Hospital Discharge Time
timeFrame: Up to Day 29
measure: Duration of Any Oxygen Use From Day 1 Through Day 29
timeFrame: Up to Day 29
measure: Mean Change From Baseline in Ordinal Scale
timeFrame: Baseline up to Day 29
measure: Absolute Change From Baseline in Ordinal Scale at Day 29
timeFrame: Baseline, Day 29
measure: Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale
timeFrame: Days 15 and 29
measure: Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)
timeFrame: Days 1, 5, 15 and 29
measure: Percentage of Participants Who Develop ARDS Distributed by Severity
timeFrame: Days 1, 5, 15 and 29
measure: Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29
timeFrame: Days 5, 15, and 29
measure: Change From Baseline in National Early Warning Score (NEWS)
timeFrame: Baseline and Day 29
measure: Percentage of Participants Achieving Clinical Response: NEWS ≤ 2 Maintained for 24 Hours
timeFrame: Day 29
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Chandler Regional Medical Center
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Wichita
country: United States
facility: Via Christi Research
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Flint
country: United States
facility: McLaren Flint
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Health Care-Macomb
state: Michigan
city: Pontiac
country: United States
facility: McLaren Health Care Oakland
state: Michigan
city: Omaha
country: United States
facility: CHI Health
state: Nebraska
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Summa Health
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network Research Institute
state: Pennsylvania
city: Tyler
country: United States
facility: CHRISTUS Health
state: Texas
city: Spokane
country: United States
facility: MultiCare Deaconess Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Tacoma General Hospital
state: Washington
Study officials:
affiliation: Wake Forest University Health Sciences
name: Simon Mahler, MD
role: PRINCIPAL_INVESTIGATOR
References: