Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza

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ClinicalTrials.gov Identifier: NCT02287467

Recruitment Status : Completed

First Posted : November 10, 2014

Results First Posted : November 14, 2019

Last Update Posted : November 14, 2019

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

University of Minnesota

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions	Influenza A Influenza B
Interventions	Biological: Intravenous hyperimmune immunoglobulin (IVIG) Biological: Placebo for IVIG
Enrollment	329

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive standard of care (SOC )treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Period Title: Overall Study
Started	168	161
Completed	156	152
Not Completed	12	9
Reason Not Completed
Protocol Violation	12	9

Baseline Characteristics

Arm/Group Title		Arm A: hIVIG	Arm B: Placebo	Total
Arm/Group Description		Participants will receive a single ...	Participants will receive a single ...	Total of all reporting groups
Arm/Group Description		Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline	Total of all reporting groups
Overall Number of Baseline Participants		156	152	308
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Participants in the analysis data set.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	156 participants	152 participants	308 participants
	<=18 years	1 0.6%	1 0.7%	2 0.6%
	Between 18 and 65 years	109 69.9%	100 65.8%	209 67.9%
	>=65 years	46 29.5%	51 33.6%	97 31.5%
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	156 participants	152 participants	308 participants
		55 (41 to 68)	57 (48 to 68)	57 (45 to 68)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	156 participants	152 participants	308 participants
	Female	80 51.3%	88 57.9%	168 54.5%
	Male	76 48.7%	64 42.1%	140 45.5%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
Race/ethnicity	Number Analyzed	156 participants	152 participants	308 participants
	Asian	33 21.2%	36 23.7%	69 22.4%
	Black/African American	27 17.3%	30 19.7%	57 18.5%
	Hispanic	27 17.3%	24 15.8%	51 16.6%
	White/Caucasian	67 42.9%	61 40.1%	128 41.6%
	Other	2 1.3%	1 0.7%	3 1.0%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	156 participants	152 participants	308 participants
United States		91 58.3%	84 55.3%	175 56.8%
United Kingdom		8 5.1%	10 6.6%	18 5.8%
Australia		5 3.2%	5 3.3%	10 3.2%
Argentina		4 2.6%	4 2.6%	8 2.6%
Denmark		5 3.2%	3 2.0%	8 2.6%
Spain		5 3.2%	5 3.3%	10 3.2%
Greece		5 3.2%	4 2.6%	9 2.9%
Mexico		1 0.6%	2 1.3%	3 1.0%
Thailand		32 20.5%	35 23.0%	67 21.8%
National Early Warning (NEW) score ^[1] Median (Inter-Quartile Range) Unit of measure: Units on a scale
	Number Analyzed	156 participants	152 participants	308 participants
		4 (2 to 6)	4 (2 to 6)	4 (2 to 6)
		[1] Measure Description: National Early Warning score measured on day of randomization. The NEW score is a morbidity index based on 6 vital signs (respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, level of consciousness). Each component is scored from 0 to 3 (best to worst) and the components are summed. Thus the composite score can range from 0 to 18.

Outcome Measures

1.Primary Outcome


Title	Number of Patients in Each of 6 Clinical Status Categories on Day 7
Description	This is the primary outcome, a 6-category ordinal outcome ranging from...
Description	This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).
Time Frame	Assessed on Day 7

Outcome Measure Data

Analysis Population Description

All infused participants, using multiple imputation to impute outcome for 4 participants with missing data.


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	156	152
Measure Type: Count of Participants Unit of Measure: Participants
Died	3 1.9%	2 1.3%
Hospitalized, in ICU	6 3.8%	11 7.2%
Non-ICU hospitalization, using supplemental oxygen	15 9.6%	16 10.5%
Non-ICU hospitalization, no supplemental oxygen	8 5.1%	12 7.9%
Discharged, not back to normal activities	56 35.9%	51 33.6%
Discharged, back to normal activities	68 43.6%	60 39.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Odds ratio of being in a better category, as assessed using a proportional odds model. Multiple imputation techniques were used to impute an outcome for 4 patients for whom the outcome was unknown.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.33
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Adjusted for baseline clinical status, region, and participation in the pilot study.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95% 0.79 to 1.97
	Estimation Comments	Odds ratio is hIVIG vs. placebo. A value greater than 1 favors the hIVIG group.

2.Secondary Outcome


Title	Number of Patients in Each of 5 Clinical Status Categories on Day 3
Description	5-category ordinal outcome assessed on day 3; clinical status ranges f...
Description	5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).
Time Frame	Assessed on Day 3

Outcome Measure Data

Analysis Population Description

All participants


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	156	152
Measure Type: Count of Participants Unit of Measure: Participants
Death	1 0.6%	0 0.0%
Hospitalized, in ICU	8 5.1%	13 8.6%
Non-ICU hospitalization, NEW score 3+	25 16.0%	31 20.4%
Non-ICU hospitalization, NEW score < 3	55 35.3%	46 30.3%
Discharged	67 42.9%	62 40.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Odds ratio for being in a better category, from a proportional odds model
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.84
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Adjusted for baseline clinical status, region, and participation in the pilot study.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95% 0.61 to 1.48
	Estimation Comments	Odds ratio is for hIVIG vs placebo. An odds ratio greater than 1 favors the hIVIG group.

3.Secondary Outcome


Title	Number of Patients in Each of 6 Clinical Status Categories on Day 3
Description	6-category ordinal outcome evaluated on Day 3; clinical status ranges ...
Description	6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).
Time Frame	Measured on Day 3

Outcome Measure Data

Analysis Population Description

All participants with clinical data available on Day 3


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	155	152
Measure Type: Count of Participants Unit of Measure: Participants
Death	1 0.6%	0 0.0%
Hospitalized, in ICU	8 5.2%	13 8.6%
Non-ICU hospitalization, on supplemental oxygen	37 23.9%	34 22.4%
Non-ICU hospitalizaiton, no supplemental oxygen	43 27.7%	43 28.3%
Discharged, not back to normal activities	53 34.2%	53 34.9%
Discharged, back to normal activities	13 8.4%	9 5.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Odds ratio for being in a better group, from a proportional odds model.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.52
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	adjusted for baseline clinical status, region, and participation in the pilot study.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95% 0.57 to 1.33
	Estimation Comments	Odds ratio is for hIVIG vs. placebo. An odds ratio > 1 favors the hIVIG group.

4.Secondary Outcome


Title	Number of Patients With a Favorable Outcome on Day 7
Description	Sliding dichotomy defined as non-ICU hospitalization or discharge if e...
Description	Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.
Time Frame	Assessed on Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	156	152
Measure Type: Count of Participants Unit of Measure: Participants
favorable outcome	128 82.1%	115 75.7%
unfavorable outcome	28 17.9%	37 24.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.20
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in the pilot study.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95% 0.81 to 2.74
	Estimation Comments	Odds ratio for hIVIG vs placebo. An odds ratio > 1.0 favors the hIVIG group.

5.Secondary Outcome


Title	Hospital Discharge
Description	Number of participants alive and discharged from the hospital
Description	Number of participants alive and discharged from the hospital
Time Frame	Measured through Day 7

Outcome Measure Data

Analysis Population Description

All participants


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	156	152
Measure Type: Count of Participants Unit of Measure: Participants
Discharged alive	119 76.3%	110 72.4%
Not discharged alive	37 23.7%	42 27.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Deaths during hospitalization are censored after day 7.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.44
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Stratified by baseline clinical status, region, and participation in the pilot study.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% .85 to 1.45
	Estimation Comments	hazard ratio is hIVIG vs placebo; a hazard ratio >1 favors the hIVIG group.

6.Secondary Outcome


Title	Mortality
Description	Number of participants dying through day 28.
Description	Number of participants dying through day 28.
Time Frame	Measured through day 28

Outcome Measure Data

Analysis Population Description

all participants


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	156	152
Measure Type: Count of Participants Unit of Measure: Participants
Died	6 3.8%	5 3.3%
Did not die	150 96.2%	147 96.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.40
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	stratified by baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.72
	Confidence Interval	(2-Sided) 95% .48 to 6.15
	Estimation Comments	hazard ratio is for hIVIG vs placebo; a hazard ratio < 1.0 favors the hIVIG group.

7.Secondary Outcome


Title	Number of Patients Alive and Out of Hospital
Description	Number and percent alive and out of hospital on day 28
Description	Number and percent alive and out of hospital on day 28
Time Frame	Measured through Day 28

Outcome Measure Data

Analysis Population Description

All participants with vital status known on Day 28


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	155	151
Measure Type: Count of Participants Unit of Measure: Participants
Alive and out of hospital	140 90.3%	137 90.7%
Died or hospitalized	15 9.7%	14 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.74
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95% .38 to 1.98
	Estimation Comments	odds ratio is for hIVIG vs placebo; an odds ratio > 1.0 favors hIVIG

8.Secondary Outcome


Title	Change in Viral Load
Description	Change in nasopharyngeal viral load from baseline to day 3
Description	Change in nasopharyngeal viral load from baseline to day 3
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

Participants with viral load results at both baseline and day 3. Participants with undetectable viral load results at baseline are excluded.


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	134	136
Mean (Standard Error) Unit of Measure: log10 RNA
	-1.99 (.16)	-2.32 (.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.49
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	Adjusted for baseline RNA, geographic region, and influenza subtype

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95% -.26 to .54
	Estimation Comments	Change is calculated as day 3 - baseline. Difference in changes is hIVIG - placebo.

9.Secondary Outcome


Title	Death or Re-hospitalization
Description	Number and percent of participants who died or were re-hospitalized af...
Description	Number and percent of participants who died or were re-hospitalized after initial discharge
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

all participants with data


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	150	146
Measure Type: Count of Participants Unit of Measure: Participants
	19 12.7%	19 13.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.93
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95% 0.5 to 1.97
	Estimation Comments	Odds ratio is for hIVIG vs placebo.

10.Secondary Outcome


Title	Percent of Participants Developing Complications
Description	Number and percent of participants developing respiratory distress syn...
Description	Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis
Time Frame	Measured through Day 28

Outcome Measure Data

Analysis Population Description

all participants


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	156	152
Measure Type: Count of Participants Unit of Measure: Participants
	20 12.8%	22 14.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.81
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.5 to 1.82
	Estimation Comments	odds ratio is for hIVIG group vs placebo

11.Secondary Outcome


Title	Number of Patients in Each of 6 Clinical Status Categories on Day 14
Description	6-category ordinal outcome measured on day 14
Description	6-category ordinal outcome measured on day 14
Time Frame	Measured on day 14

Outcome Measure Data

Analysis Population Description

participants with observed data on day 14


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	152	151
Measure Type: Count of Participants Unit of Measure: Participants
Died	4 2.6%	4 2.6%
Hospitalized in ICU	5 3.3%	6 4.0%
Hospitalized on supplement oxygen	8 5.3%	5 3.3%
Hospitalized not on supplemental oxygen	4 2.6%	11 7.3%
Discharged, not back to normal activities	29 19.1%	33 21.9%
Discharged, back to normal activities	102 67.1%	92 60.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Proportional odds for being in a better category
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.55
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in the pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95% 0.70 to 1.95
	Estimation Comments	Odds ratio (hIVIG vs placebo) of being in a better category. An odds ratio > 1 favors the hIVIG group.

12.Secondary Outcome


Title	Number of Patients Alive and Out of Hospital on Day 14
Description	Number and percentage of participants alive and out of the hospital on...
Description	Number and percentage of participants alive and out of the hospital on Day 14
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

all participants


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	155	151
Measure Type: Count of Participants Unit of Measure: Participants
	134 86.5%	125 82.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.77
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% .5 to 2.31
	Estimation Comments	odds ratio is for hIVIG vs placebo

13.Secondary Outcome


Title	Resumption of Normal Activities by Day 14
Description	Participants reporting resumption of normal daily activities by Day 14
Description	Participants reporting resumption of normal daily activities by Day 14
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

Participants with observed data


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	152	151
Measure Type: Count of Participants Unit of Measure: Participants
	102 67.1%	92 60.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.34
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95% 0.7 to 2.34
	Estimation Comments	odds ratio is expressed as hIVIG vs placebo

14.Secondary Outcome


Title	Number of Patients in Each of 6 Clinical Status Categories on Day 28
Description	6-category ordinal outcome corresponding to clinical status on day 28
Description	6-category ordinal outcome corresponding to clinical status on day 28
Time Frame	day 28

Outcome Measure Data

Analysis Population Description

participants with observed data


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	151	150
Measure Type: Count of Participants Unit of Measure: Participants
Died	6 4.0%	5 3.3%
Hospitalized in ICU	2 1.3%	2 1.3%
Hospitalized, on supplemental oxygen	6 4.0%	2 1.3%
Hospitalized, not on supplemental oxygen	1 0.7%	5 3.3%
Discharged, not back to normal activities	21 13.9%	22 14.7%
Discharged, back to normal activities	115 76.2%	114 76.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.73
	Comments	adjusted for baseline clinical status, region, and participation in pilot study
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	.90
	Confidence Interval	(2-Sided) 95% .50 to 1.62
	Estimation Comments	odds ratio (hIVIG vs placebo) is for being in a better category. An odds ratio >1 favors the hIVIG group.

15.Secondary Outcome


Title	Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Description	Primary 6-category ordinal outcome for participants infected with Infl...
Description	Primary 6-category ordinal outcome for participants infected with Influenza A
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

all participants infected with influenza A


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	114	110
Measure Type: Count of Participants Unit of Measure: Participants
Died	3 2.6%	0 0.0%
Hospitalized in ICU	5 4.4%	7 6.4%
Hospitalized on supplemental oxygen	14 12.3%	9 8.2%
Hospitalized not on supplemental oxygen	7 6.1%	10 9.1%
Discharged, not back to normal activities	40 35.1%	39 35.5%
Discharged, back to normal activities	45 39.5%	45 40.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Multiple imputation was used to estimate the outcome for 3 participants for whom the outcome was partially unknown.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.82
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in the pilot study.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.55 to 1.59
	Estimation Comments	Odds ratio (hIVIG vs placebo) is for being in a better category.

16.Secondary Outcome


Title	Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Description	Primary 6-category ordinal outcome for subgroup of participants infect...
Description	Primary 6-category ordinal outcome for subgroup of participants infected with influenza B
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	42	42
Measure Type: Count of Participants Unit of Measure: Participants
Died	0 0.0%	2 4.8%
Hospitalized in ICU	1 2.4%	4 9.5%
Hospitalized on supplemental oxygen	1 2.4%	7 16.7%
Hospitalized not on supplemental oxygen	1 2.4%	2 4.8%
Discharged, not back to normal activities	16 38.1%	12 28.6%
Discharged, back to normal activities	23 54.8%	15 35.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	Multiple imputation was used to estimate the outcome for one participant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.02
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	adjusted for baseline clinical status, region, and participation in pilot study

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.19
	Confidence Interval	(2-Sided) 95% 1.21 to 8.42
	Estimation Comments	Odds ratio (hIVIG vs placebo) for a better outcome. An odds ratio > 1 favors the hIVIG group.

17.Secondary Outcome


Title	pH1N1 Titers at Day 7
Description	pH1N1 hemagglutination inhibition assay (HAI) titers among participant...
Description	pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

participants infected with pH1N1 with HAI titers measured at day 7


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	23	26
Mean (Standard Deviation) Unit of Measure: titer
	285 (374)	229 (341)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	HAI measurements were log-transformed to compute treatment differences and the model was adjusted for baseline titer.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.18
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	longitudinal regression with adjustment for baseline titer

Method of Estimation	Estimation Parameter	ratio of geometric means
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95% 0.84 to 2.7
	Estimation Comments	Ratio of hIVIG group to placebo group. A ratio > 1.0 indicates higher titers for the hIVIG group.

18.Secondary Outcome


Title	H3N2 Titers at Day 7
Description	H3N2 HAI titers among participants infected with H3N2 using A/HongKong...
Description	H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

participants infected with H3N2 with HAI titers measured at day 7


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	54	49
Mean (Standard Deviation) Unit of Measure: titer
	259 (291)	225 (277)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.13
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	longitudinal analysis of log-transformed titers adjust for baseline titer.

Method of Estimation	Estimation Parameter	ratio of geometric means
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95% 0.93 to 1.8
	Estimation Comments	Ratio of geometric means of hIVIG vs placebo. A ratio >1.0 indicates higher titers in the hIVIG group on day 7.

19.Secondary Outcome


Title	Influenza B Titers at Day 7
Description	Flu B HAI titers among participants infected with influenza B using B/...
Description	Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

participants infected with influenza B with HAI titers measured at day 7


Arm/Group Title	Arm A: hIVIG	Arm B: Placebo
Arm/Group Description:	Participants will receive a single ...	Participants will receive a single ...
Arm/Group Description:	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
Overall Number of Participants Analyzed	39	40
Mean (Standard Deviation) Unit of Measure: titer
	112 (161)	84 (83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: hIVIG, Arm B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.78
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	log-transformed titers adjusted for baseline titer

Method of Estimation	Estimation Parameter	ratio of geometric means
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.58 to 1.5
	Estimation Comments	ratio of geometric mean for hIVIG vs placebo. A ratio > 1.0 indicates higher titers at day 7 for the hIVIG group.

Adverse Events

Time Frame	28 days
Adverse Event Reporting Description	Serious adverse events plus all grade 3 and 4 adverse events, as graded according to the National Institute of Health Division of AIDS (DAIDS) toxicity table.

Arm/Group Title	Arm A: hIVIG		Arm B: Placebo
Arm/Group Description	Participants will receive a single ...		Participants will receive a single ...
Arm/Group Description	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)		Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
All-Cause Mortality
	Arm A: hIVIG		Arm B: Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	6/156 (3.85%)		5/152 (3.29%)
Serious Adverse Events Serious Adverse Events
	Arm A: hIVIG		Arm B: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/156 (16.03%)		26/152 (17.11%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Leukopenia ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Cardiac disorders
Acute myocardial infarction ^† 1	2/156 (1.28%)	2	0/152 (0.00%)	0
Atrial fibrillation ^† 1	0/156 (0.00%)	0	2/152 (1.32%)	2
Cardiac failure ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Gastrointestinal disorders
Internal hernia ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Nausea ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Retroperitoneal haemorrhage ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Vomiting ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Infections and infestations
Breast abscess ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Enterococcal bacteraemia ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Influenza ^† 1	2/156 (1.28%)	2	0/152 (0.00%)	0
Pneumonia ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Pneumonia bacterial ^† 1	1/156 (0.64%)	1	1/152 (0.66%)	1
Pneumonia fungal ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Pyelonephritis ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Sepsis ^† 1	1/156 (0.64%)	1	1/152 (0.66%)	1
Septic shock ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Injury, poisoning and procedural complications
Post lumbar puncture syndrome ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Rib fracture ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Road traffic accident ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Investigations
Blood creatinine increased ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Metabolism and nutrition disorders
Dehydration ^† 1	1/156 (0.64%)	1	1/152 (0.66%)	1
Fluid overload ^† 1	1/156 (0.64%)	2	0/152 (0.00%)	0
Hyperkalaemia ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Hypoglycaemia ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Nervous system disorders
Dizziness ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Haemorrhage intracranial ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Headache ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Vocal cord paresis ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Psychiatric disorders
Dysthymic disorders ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	0/156 (0.00%)	0	2/152 (1.32%)	2
Renal failure ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Acute respiratory failure ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Aspiration ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Asthma ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Bronchospasm ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Chronic obstructive pulmonary disease ^† 1	1/156 (0.64%)	1	5/152 (3.29%)	8
Dyspnoea ^† 1	1/156 (0.64%)	1	1/152 (0.66%)	1
Hypoxia ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Pleural effusion ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Pneumonia aspiration ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Pulmonary embolism ^† 1	2/156 (1.28%)	2	0/152 (0.00%)	0
Pulmonary oedema ^† 1	1/156 (0.64%)	1	0/152 (0.00%)	0
Respiratory distress ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Respiratory failure ^† 1	1/156 (0.64%)	1	2/152 (1.32%)	2
Skin and subcutaneous tissue disorders
Diabetic foot ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Vascular disorders
Hypotension ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
Thrombophlebitis superficial ^† 1	0/156 (0.00%)	0	1/152 (0.66%)	1
1 Term from vocabulary, MedDRA 21.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Arm A: hIVIG		Arm B: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/156 (8.33%)		14/152 (9.21%)
Investigations
Blood creatinine increased ^† 1	4/156 (2.56%)	5	1/152 (0.66%)	1
Haemoglobin decreased ^† 1	2/156 (1.28%)	4	4/152 (2.63%)	6
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	1/156 (0.64%)	1	4/152 (2.63%)	4
Musculoskeletal and connective tissue disorders
Myalgia ^† 1	2/156 (1.28%)	2	4/152 (2.63%)	4
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	5/156 (3.21%)	5	4/152 (2.63%)	4
Dyspnoea ^† 1	4/156 (2.56%)	5	3/152 (1.97%)	3
1 Term from vocabulary, MedDRA 21.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dr. Richard Davey
Organization:	NIAID
Phone:	301-496-8029
EMail:	rdavey@niaid.nih.gov

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Davey RT Jr, Fernandez-Cruz E, Markowitz N, Pett S, Babiker AG, Wentworth D, Khurana S, Engen N, Gordin F, Jain MK, Kan V, Polizzotto MN, Riska P, Ruxrungtham K, Temesgen Z, Lundgren J, Beigel JH, Lane HC, Neaton JD; INSIGHT FLU-IVIG Study Group. Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial. Lancet Respir Med. 2019 Nov;7(11):951-963. doi: 10.1016/S2213-2600(19)30253-X. Epub 2019 Sep 30.

Layout table for additonal information

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT02287467
Other Study ID Numbers:	INSIGHT 006: FLU-IVIG
First Submitted:	November 6, 2014
First Posted:	November 10, 2014
Results First Submitted:	September 20, 2019
Results First Posted:	November 14, 2019
Last Update Posted:	November 14, 2019

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