Clinical trial NCT04432324: Study to Evaluate the Safety and Efficacy of High Dose IVIG in Hospitalized Participants 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 Hospitalized Subjects With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus Disease
Severe acute respiratory syndrome coronavirus 2
SARS-CoV-2
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2020-06-16
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 high dose Intravenous IVIG plus SMT can reduce the proportion of participants dying or requiring intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical ventilation on Day 29 versus SMT alone in hospitalized participants with COVID-19.


Eligibility criteria: Inclusion Criteria:

1. Hospitalized male or female subject ≥ 18 years of age at time of Screening who is being treated for COVID-19.
2. Has laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by qualitative Polymerase Chain Reaction (PCR) (reverse transcriptase \[RT\]-PCR), or other commercial or public health assay (of any type) in any specimen during the current hospital admission prior to randomization.
3. COVID-19 illness (symptoms) of any duration with radiographic infiltrates by imaging (Chest X-Ray, Computed tomography (CT) scan, etc.).
4. PaO2/FIO2 ratio \> 300 to ≤ 450 mmHg (i.e., arterial oxygen in mmHg divided by fraction inspired oxygen concentration \[e.g., 0.21 for room air\])
5. 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).
6. Subject (or a legal representative or a nearest relative or a relative by marriage, as appropriate) provides oral informed consent prior to initiation of any study procedures.

Exclusion criteria:

1. Subject requires invasive mechanical ventilation or ICU admission.
2. Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator may place the subject at undue medical risk.
3. The subject has had a known (documented) serious anaphylactic reaction to blood, any blood-derived or plasma product or commercial immunoglobulin.
4. Subject has known (documented) hereditary fructose intolerance (HFI).
5. A medical condition in which the infusion of additional fluid is contraindicated.
6. 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.
7. Subject with known (documented) thrombotic complications to polyclonal IVIG therapy in the past.
8. Subject with current or prior (within the past 1 month) myocardial infarction, stroke, deep vein thrombosis, or thromboembolic event.
9. Subject with limitations of therapeutic effort (eg, 'do not resuscitate' status).
10. Female subject 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.
11. Subject participating in another interventional clinical trial with investigational medical product or device.

Primary outcomes:
measure: Percentage of Participants Dying or Requiring ICU Admission
timeFrame: Up to Day 29
measure: Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation
timeFrame: Day 29
Secondary outcomes:
measure: Change from Baseline in National Early Warning Score (NEWS)
timeFrame: Day 1 through Day 29
measure: Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours
timeFrame: Day 1 through Day 29
measure: Time to Hospital Discharge
timeFrame: Day 1 through Day 29
measure: Duration of ICU Stay
timeFrame: Up to Day 29
measure: Duration of Any Oxygen Use
timeFrame: Day 1 through Day 29
measure: Duration of Mechanical Ventilation
timeFrame: Up to Day 29
measure: Mean Change from Baseline in Ordinal Scale
timeFrame: Day 1 through Day 29
measure: Absolute Value Change from Baseline in Ordinal Scale
timeFrame: Day 1 through Day 29
measure: Length of Time to Clinical Progression
timeFrame: Up to Day 29
measure: Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale
timeFrame: Day 15 and Day 29
measure: Time to Sustained Normalization of Temperature
timeFrame: Day 1 through Day 29
measure: Percentage of Participants with Normalization of Fever
timeFrame: Day 1 through Day 29
measure: Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)
timeFrame: Day 29
Other outcomes:
Locations:
city: San Sebastián De Los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofía
state: Madrid
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
Study officials:
References: