Intravenous Immunoglobulin (IVIG) in Lung Transplantation

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00115778
• Collaborator: Grifols Therapeutics LLC (Industry)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 62
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if intravenous immunoglobulin (IVIG) can prevent bacterial infections in lung transplant patients with low serum levels of immunoglobulin.

Condition or Disease	Intervention/Treatment	Phase
Hypogammaglobulinemia; Lung Transplantation	Drug: IVIG; Other: Placebo	Phase 2

Detailed Description

An increased risk of infection despite intensive antimicrobial prophylaxis is a well-recognized complication of lung transplantation. Recent evidence suggests that immunosuppressive therapy after solid organ transplantation may lead to humoral immunodeficiency due to hypogammaglobulinemia (HGG). In lung transplant recipients with HGG, IVIG therapy offers the potential to significantly decrease the incidence and severity of infections, thereby reducing morbidity and potentially mortality.

Comparison: The investigators are conducting a randomized clinical trial of IVIG versus placebo for lung transplant patients with severe HGG to see if IVIG decreases the number of bacterial infections in these patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: IVIG for Acquired Immunodeficiency in Lung Transplant Patients
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: First IVIG, then Placebo Study participants will receive three doses of IVIG given four weeks apart over 12 weeks followed by a twelve-week washout and then three doses of placebo over 12 weeks.	Drug: IVIG; 10% Caprylate/Chromatography Purified Intravenous Immunoglobulin 400 mg/kg IV every 4 weeks; Other Names: Immune globulin intravenous Gamunex Intravenous immunoglobulin ; Other: Placebo; 0.1% Albumin in an equal volume to the investigational product
Experimental: First Placebo, then IVIG Study participants will receive three doses of 0.1% albumin solution (placebo) given four weeks apart over 12 weeks followed by a twelve-week washout and then three doses of IVIG over 12 weeks.	Drug: IVIG; 10% Caprylate/Chromatography Purified Intravenous Immunoglobulin 400 mg/kg IV every 4 weeks; Other Names: Immune globulin intravenous Gamunex Intravenous immunoglobulin ; Other: Placebo; 0.1% Albumin in an equal volume to the investigational product

Outcome Measures

Primary Outcome Measures

1. Number of Clinically Diagnosed Bacterial Infections During the Treatment Period [3 month]

   The number of events occurring during the treatment period. The data will be presented by the occurrence during the IVIG vs. the placebo treatment period, regardless of the order that the treatment was received. Only the clinically diagnosed bacterial infections will be counted.

Secondary Outcome Measures

1. Number of Clinically Diagnosed Viral Infections [3 month]

   This is to measure the effect of IVIG on viral infections.

2. Number of Hospital Admissions [3 month]

   This is to measure the effect of IVIG on hospitalizations.

3. Number of Antibiotic Initiation [3 month]

   This is to measure the effect of IVIG on the use of antibiotics.

4. Number of Clinically Diagnosed Fungal Infection [3 months]

   This is to measure the effect of IVIG on fungal infections.

5. Number of Lymphocytic Bronchiolitis [3 months]

   This is to measure the effect of IVIG on lung function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Lung transplant recipients > 3 months after transplant surgery

• Immunoglobulin G (IgG) < 500 mg/dL

• Stable medical regimen

Exclusion Criteria:

• Acute rejection

• Active infection

• Contraindication to IVIG

• Pregnancy

• Recent thrombotic event

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York Presbyterian Hospital Lung Transplant Program	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• Grifols Therapeutics LLC

Investigators

• Principal Investigator: Selim M Arcasoy, M.D., Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Selim Arcasoy, Dickinson W. Richards, Jr. Professor of Medicine (in Pediatrics) at the Columbia University Medical Center, Dept of Medicine Pulmonary, Columbia University
• ClinicalTrials.gov Identifier: NCT00115778
• Other Study ID Numbers: AAAB0431
• First Posted: Jun 27, 2005
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• 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 Selim Arcasoy, Dickinson W. Richards, Jr. Professor of Medicine (in Pediatrics) at the Columbia University Medical Center, Dept of Medicine Pulmonary, Columbia University: Hypogammaglobulinemia; Lung Transplantation
• Additional relevant MeSH terms: Agammaglobulinemia; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin

Study Results

Participant Flow

Pre-assignment Detail	Eleven subjects were eligible and randomized, and 10 completed all study assessments. One subject discontinued the interventions because of inability to comply with the schedule of study visits. 10 subjects are needed to detect a reduction in the mean number of bacterial infections/patient by one standard deviation over three months with 80% power.

Arm/Group Title	Group 1: Placebo Then IVIG	Group: 2 IVIG Then Placebo
Arm/Group Description	Study participants consented to receive three doses of 0.1% albumin solution (placebo) given four weeks apart over 12 weeks (period 1) followed by a twelve-week washout and then three doses of IVIG over 12 weeks (period 2). Period 1 (12 weeks) Washout period (12 weeks) Period 2 (12 weeks) Analysis: modified intention-to-treat	Study participants consented to receive three doses of IVIG given four weeks apart over 12 weeks (period 1) followed by a twelve-week washout and then three doses of placebo over 12 weeks (period 2). Period 1 (12 weeks) Washout period (12 weeks) Period 2 (12 weeks) Analysis: modified intention-to-treat
Period Title: Overall Study
STARTED	6	5
COMPLETED	6	4
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Study participants consented to receive three doses of IVIG (or 0.1% albumin solution (placebo)) given four weeks apart followed by a twelve-week washout and then three doses of placebo (or IVIG).
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 81.8%
>=65 years	2 18.2%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	5 45.5%
Male	6 54.5%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Number of Clinically Diagnosed Bacterial Infections During the Treatment Period
Description	The number of events occurring during the treatment period. The data will be presented by the occurrence during the IVIG vs. the placebo treatment period, regardless of the order that the treatment was received. Only the clinically diagnosed bacterial infections will be counted.
Time Frame	3 month

Outcome Measure Data

Analysis Population Description

The crossover design, in which each subject serves as his or her own control, allows sufficient power for the detection of a clinically significant effect of IVIG with only a small number of patients. A sample size of 10 patients in a crossover trial has more power to detect differences than double the sample size using a parallel design.

Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2	Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).	Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
Measure Participants	10	10
Number [Infections]	3	1

2. Secondary Outcome

Title	Number of Clinically Diagnosed Viral Infections
Description	This is to measure the effect of IVIG on viral infections.
Time Frame	3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2	Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).	Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
Measure Participants	10	10
Number [Number of Infections]	2	2

3. Secondary Outcome

Title	Number of Hospital Admissions
Description	This is to measure the effect of IVIG on hospitalizations.
Time Frame	3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2	Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).	Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
Measure Participants	10	10
Number [Admissions]	3	1

4. Secondary Outcome

Title	Number of Antibiotic Initiation
Description	This is to measure the effect of IVIG on the use of antibiotics.
Time Frame	3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2	Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).	Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
Measure Participants	10	10
Number [Uses of antibiotics]	9	8

5. Secondary Outcome

Title	Number of Clinically Diagnosed Fungal Infection
Description	This is to measure the effect of IVIG on fungal infections.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2	Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).	Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
Measure Participants	10	10
Number [Infections]	2	0

6. Secondary Outcome

Title	Number of Lymphocytic Bronchiolitis
Description	This is to measure the effect of IVIG on lung function.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2	Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).	Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
Measure Participants	10	10
Number [Instances of bronchiolitis]	0	0

Adverse Events

Time Frame	3 months
Arm/Group Title	Participants Receiving IVIG During Period 1 or Period 2		Participants Receiving Placebo During Period 1 or Period 2
Arm/Group Description	Study participants received three doses of IVIG first (Period 1) or second (Period 2 - after a twelve-week washout).		Study participants received three doses of placebo first (Period 1) or second (Period 2 - after a twelve-week washout).
All Cause Mortality
	Participants Receiving IVIG During Period 1 or Period 2		Participants Receiving Placebo During Period 1 or Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Participants Receiving IVIG During Period 1 or Period 2		Participants Receiving Placebo During Period 1 or Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		1/10 (10%)
Eye disorders
Vitreous hemorrhage	1/10 (10%)	1	0/10 (0%)	0
Gastrointestinal disorders
Pancreatitis	1/10 (10%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
E. coli pneumonia	1/10 (10%)	1	0/10 (0%)	0
Surgical and medical procedures
Hospital admission for thymoglobulin infusion	0/10 (0%)	0	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Participants Receiving IVIG During Period 1 or Period 2		Participants Receiving Placebo During Period 1 or Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		6/10 (60%)
Gastrointestinal disorders
Diarrhea	0/10 (0%)		2/10 (20%)
Abdominal discomfort	1/10 (10%)		2/10 (20%)
General disorders
Fever	2/10 (20%)		0/10 (0%)
Night sweats	0/10 (0%)		2/10 (20%)
Headache	2/10 (20%)		3/10 (30%)
Musculoskeletal and connective tissue disorders
Pedal edema	0/10 (0%)		3/10 (30%)
Stiff neck	2/10 (20%)		0/10 (0%)
Musculoskeletal pain	2/10 (20%)		2/10 (20%)
Renal and urinary disorders
Urinary frequency	1/10 (10%)		2/10 (20%)
Respiratory, thoracic and mediastinal disorders
Cough	2/10 (20%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.