Study of SOC Plus IVIG Compared to SOC Alone in the Treatment of COVID-19

• Sponsor: George Sakoulas, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT04411667
• Collaborator: Octapharma (Industry)
• Enrollment: 34
• Locations: 2
• Arms: 2
• Actual Duration (Months): 1.8
• Patients Per Site: 17
• Patients Per Site Per Month: 9.2

Study Details

Study Description

Brief Summary

The purpose of this research is to see if Intravenous Immunoglobulin (IVIG) can help reduce respiratory complications (respiratory failure and need for a ventilator) caused by coronavirus disease 2019 (COVID-19). The principal investigator has successfully utilized IVIG for patients infected with the influenza virus. The investigator wants to find out if IVIG is equally effective in COVID-19 infection patients, and if IVIG will give the immune system some help to clear the infection naturally.

Condition or Disease	Intervention/Treatment	Phase
Sars-CoV2	Drug: Octagam	Phase 4

Detailed Description

This is an investigator initiated, open label, multicenter, two arm, randomized study to compare the impact of adding IVIG to the Standard of Care (SOC) to the SOC without IVIG. Randomization will be 1:1. The goal of this study is to identify whether or not IVIG can halt the progression to respiratory failure requiring mechanical ventilation in subjects admitted to the hospital with confirmed COVID-19. The addition of IVIG to the standard of care treatment for these patients may be beneficial in abating acute lung injury in subjects with SARSCoV-2 induced hypoxia that results in organ injury.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized into one of two groups: Standard of Care plus IVIG or Standard of Care.Subjects will be randomized into one of two groups: Standard of Care plus IVIG or Standard of Care.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Open Label Study of Standard of Care Plus Intravenous Immunoglobulin (IVIG) Compared to Standard of Care Alone in the Treatment of COVID-19 Infection
• Actual Study Start Date: Apr 28, 2020
• Actual Primary Completion Date: Jun 23, 2020
• Actual Study Completion Date: Jun 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (study drug+SOC) Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated.	Drug: Octagam; Standard of Care plus Octagam infusion for 3 days.; Other Names: IVIG
No Intervention: Group B (SOC) Standard of Care

Outcome Measures

Primary Outcome Measures

1. Mechanical Ventilation [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Number of subjects requiring mechanical ventilation due to respiratory failure

Secondary Outcome Measures

1. Oxygen Therapy [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days]

   Number of days requiring oxygen therapy

2. Length of Stay [from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 60 days]

   Number of days in hospital

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed COVID-19 positive test result (including presumptive positive).

• Hospitalization

• Requiring ≥4 liters/min O2 nasal cannula to maintain oxygen saturation ≥ 92%, but not mechanically ventilated

• Age ≥18 years old.

• Access to a phone in the hospital room or an electronic device that is capable of receiving phone calls and/or video calls and/or e-mail.

• Able to read/write/speak English or Spanish fluently.

• Subjects must have the capacity to provide consent or an appropriate Legally Authorized Representative (LAR) to provide informed consent.

provide informed consent, and provide authorization of use and disclosure of personal health information.

• Negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

• Severe allergy to any IVIG product formulation

• History of DVT, PE, thromboembolic stroke or other thrombotic events

• Hypersensitivity to corn. Octagam® contains maltose which is a sugar derived from corn.

• Uncontrolled hypertension (SBP>180 mm Hg or DBP>120mmHg)

• Active participant in another research treatment study

• Mechanically ventilated patient

• Code status is Do Not Resuscitate or Do Not Intubate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sharp Grossmont Hospital	La Mesa	California	United States	91942
2	Sharp Memorial Hospital	San Diego	California	United States	92123

Sponsors and Collaborators

• George Sakoulas, MD
• Octapharma

Investigators

• Principal Investigator: George Sakoulas, MD, Sharp HealthCare

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 19, 2020

More Information

Publications

None provided.

• Responsible Party: George Sakoulas, MD, Infectious Disease Specialist, Sharp HealthCare
• ClinicalTrials.gov Identifier: NCT04411667
• Other Study ID Numbers: COVID-IVIG; 2004902
• First Posted: Jun 2, 2020
• Last Update Posted: Jun 25, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by George Sakoulas, MD, Infectious Disease Specialist, Sharp HealthCare: Coronavirus; IVIG; COVID-19
• Additional relevant MeSH terms: COVID-19; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Study Results

Participant Flow

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated. Octagam: Standard of Care plus Octagam infusion for 3 days.	Standard of Care
Period Title: Overall Study
STARTED	17	17
COMPLETED	16	17
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)	Total
Arm/Group Description	Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated. Octagam: Standard of Care plus Octagam infusion for 3 days.	Standard of Care	Total of all reporting groups
Overall Participants	16	17	33
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54	54	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	51	56
Sex: Female, Male (Count of Participants)
Female	6 37.5%	7 41.2%	13 39.4%
Male	10 62.5%	10 58.8%	20 60.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 81.3%	15 88.2%	28 84.8%
Not Hispanic or Latino	3 18.8%	2 11.8%	5 15.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Body Mass Index (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	32.5	34.9	33.6
Comorbidities (Count of Participants)
Diabetes mellitus	6 37.5%	6 35.3%	12 36.4%
Hypertension	4 25%	7 41.2%	11 33.3%
Chronic kidney disease	0 0%	1 5.9%	1 3%
Coronary artery disease	1 6.3%	1 5.9%	2 6.1%
Congestive heart failure	1 6.3%	1 5.9%	2 6.1%
Asthma/chronic obstructive pulmonary disease	2 12.5%	2 11.8%	4 12.1%
Current smoker	1 6.3%	1 5.9%	2 6.1%
Former smoker	2 12.5%	1 5.9%	3 9.1%
Immunocompromised	1 6.3%	0 0%	1 3%
Comorbidities Continued (HbA1c) (% glycosylated hemoglobin) [Mean (Full Range) ]
Mean (Full Range) [% glycosylated hemoglobin]	10.1	6.4	8.1
Other Coronavirus Disease 2019 Therapies (Count of Participants)
Remdesivir	8 50%	9 52.9%	17 51.5%
Convalescent plasma	2 12.5%	3 17.6%	5 15.2%
Glucocorticoids	16 100%	10 58.8%	26 78.8%

Outcome Measures

1. Primary Outcome

Title	Mechanical Ventilation
Description	Number of subjects requiring mechanical ventilation due to respiratory failure
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated. Octagam: Standard of Care plus Octagam infusion for 3 days.	Standard of Care
Measure Participants	16	17
Count of Participants [Participants]	2 12.5%	7 41.2%

2. Secondary Outcome

Title	Oxygen Therapy
Description	Number of days requiring oxygen therapy
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days

Outcome Measure Data

Analysis Population Description

This data was not collected although it was originally intended to be an outcome measure

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated. Octagam: Standard of Care plus Octagam infusion for 3 days.	Standard of Care
Measure Participants	0	0

3. Secondary Outcome

Title	Length of Stay
Description	Number of days in hospital
Time Frame	from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (Study Drug+SOC)	Group B (SOC)
Arm/Group Description	Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated. Octagam: Standard of Care plus Octagam infusion for 3 days.	Standard of Care
Measure Participants	16	17
Median (Full Range) [days]	12	17

Adverse Events

Time Frame	from date of patient enrollment to date of patient discharge or date of death, whichever came first, assessed up to 45 days
Arm/Group Title	Group A (Study Drug+SOC)		Group B (SOC)
Arm/Group Description	Standard of care plus IVIG (Octagam) 0.5g/kg IVPB actual body weight daily x 3 days, with premedication methylprednisolone 40 mg IV push x 1 30-50 minutes before each IVIG infusion. Initial infusion rate of IVIG (Octagam) will be of 0.6 mL/kg/hour, increasing to a maximum rate of 100ml/hr, if tolerated. Octagam: Standard of Care plus Octagam infusion for 3 days.		Standard of Care
All Cause Mortality
	Group A (Study Drug+SOC)		Group B (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		3/17 (17.6%)
Serious Adverse Events
	Group A (Study Drug+SOC)		Group B (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Group A (Study Drug+SOC)		Group B (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)		8/17 (47.1%)
General disorders
Elevated D-Dimer	2/16 (12.5%)	2	2/17 (11.8%)	2
Elevated Liver Function Tests	3/16 (18.8%)	3	0/17 (0%)	0
Hyperglycemia	3/16 (18.8%)	3	2/17 (11.8%)	2
Thrombocytosis	1/16 (6.3%)	1	1/17 (5.9%)	1
Anemia	0/16 (0%)	0	3/17 (17.6%)	3
Leukocytosis	1/16 (6.3%)	1	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Acute Hypoxic Respiratory Failure	1/16 (6.3%)	1	1/17 (5.9%)	1

Limitations/Caveats

Study limited to two hospitals in one US city. Resulted in a homogenous population of younger Hispanic/Latino patients. Study was not blinded. Methylprednisolone was used as a pre-medication for each dose of IVIG which may have confounded the results. Small sample size.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.