Aralast alpha1-proteinase Inhibitor Surveillance Study - Full Text View

Sponsor:	Baxter Healthcare Corporation
Information provided by (Responsible Party):	Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT00313144

Purpose

The primary objectives of this Phase 4, open label, prospective U.S. surveillance study are to evaluate the health outcomes of Alpha 1-Antitrypsin (AAT)-deficient subjects who are initiating treatment with ARALAST on patient-related outcomes (PRO), i.e., health-related quality of life (HRQoL), healthcare resource utilization (HCRU), and various laboratory analyses to evaluate the safety of long-term administration of ARALAST.

Up to 120 subjects will be enrolled and assessed for HRQoL and HCRU at baseline and every 6-months thereafter, for 2 years. A subset of subjects will be enrolled into the blood draw portion of the study, which will also include assessments of antibodies to ARALAST, and chemistry panel. Subjects will be treated according to the prescribing (attending) physician's instructions based on the prescribing information given in the ARALAST package insert.

Condition	Intervention	Phase
Alpha 1-Antitrypsin (AAT) Deficiency	Drug: ARALAST Alpha1-Proteinase Inhibitor	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	ARALAST alpha1-proteinase Inhibitor (α1-PI) Surveillance Study

Resource links provided by NLM:

Genetics Home Reference related topics: alpha-1 antitrypsin deficiency

MedlinePlus related topics: Alpha-1 Antitrypsin Deficiency

U.S. FDA Resources

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:

HRQoL 'Physical Functioning (PF)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Role Limitation Due to Physical Health (RP)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Bodily Pain (BP)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'General Health (GH)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Vitality (VT)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Social Functioning (SF)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Role Limitation Due to Emotional Problems (RE)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Mental Health (MH)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL 'Physical Component Score (PCS)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
SF-36 scores for baseline (screening) versus the period from baseline to ≤6 Months. The PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores.
HRQoL 'Mental Component Score (MCS)' From Baseline to ≤6 Months [ Time Frame: Screening to ≤ 6 Months ] [ Designated as safety issue: No ]
SF-36 scores for baseline (screening) versus the period from baseline to ≤6 Months. The MCS is a summary scale of the dimensions vitality, social functioning, role emotional, and mental health Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores.
HRQoL For: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS: Baseline, Baseline to ≤6 Months, and >6 Months to ≤12 Months [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: No ]
SF-36 Scores- baseline thru 12 months, where data was available. Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The Data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL for PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS Scores: Baseline, Baseline to ≤6 Months, >6 Months to ≤12 Months, and >12 Months to ≤18 Months [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: No ]
SF-36 Scores- baseline thru 12 months, where data was available. Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The Data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.
HRQoL for PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS Scores: Baseline, Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: No ]
SF-36 Scores- baseline thru 24 months, where data was available. Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The Data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000.

Secondary Outcome Measures:

Healthcare Resource Utilization (HCRU) 'Frequency of Emergency Room (ER) Visits' [ Time Frame: Baseline to 24 Months ] [ Designated as safety issue: Yes ]
Number of participants with indicated number of ER visits (0, 1, 2, 3, ≥4 ER visits per participant) during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Mean Number of Emergency Room (ER) Visits' [ Time Frame: One year prior to baseline to 24 months post-baseline ] [ Designated as safety issue: Yes ]
Mean number of ER visits one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Frequency of Hospitalizations' [ Time Frame: Baseline to 24 Months ] [ Designated as safety issue: Yes ]
Number of participants with indicated number of hospitalizations during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Mean Length of Stay (LOS) in Hospital' [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: Yes ]
Mean LOS during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Number of Participants Taking Antibiotics' [ Time Frame: One year prior to baseline to 24 months post-baseline ] [ Designated as safety issue: No ]
Number of participants taking antibiotics one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Number of Antibiotic Courses' [ Time Frame: One year prior to baseline to 24 months post-baseline ] [ Designated as safety issue: No ]
Number of antibiotic courses (i.e. number of antibiotic prescriptions) one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Number of Participants Receiving Steroid Pulse Courses' [ Time Frame: One year prior to baseline to 24 months post-baseline ] [ Designated as safety issue: No ]
Number of participants receiving steroid pulse courses (i.e. number of steroid prescriptions) one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Healthcare Resource Utilization (HCRU) 'Number of Steroid Pulse Courses' [ Time Frame: One year prior to baseline to 24 months post-baseline ] [ Designated as safety issue: No ]
Number of steroid pulse courses (i.e. number of steroid prescriptions) one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Hepatic Chemistry Parameters: Change From Baseline/Screening [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: Yes ]
Summary of changes in hepatic (total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase) parameters from screening/baseline through each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
Renal and Hepatic Chemistry Parameters: Change From Baseline/Screening [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: Yes ]
Summary of changes in hepatic (total bilirubin) and renal (Blood urea nitrogen (BUN), creatinine) parameters from screening/baseline through each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months)
ARALAST Antibody Titers: Participants With at Least 2-Dilution Step Increases From Screening [ Time Frame: Baseline to 24 Months ] [ Designated as safety issue: Yes ]
All IgG and IgM titers at screening were ≤ 4. A 2-dilution step increase was defined as follows:
- The titer at each 6-month visit must be ≥ 4 when the screening titer = 0
- Each 6-month visit titer / screening titer should be ≥ 4. 6 month window periods are: baseline to ≤6 months, >6 months to ≤12 months, >12 months to ≤18 months, and >18 months to ≤24 months

Enrollment:	127
Study Start Date:	June 2006
Study Completion Date:	May 2009
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Weekly ARALAST infusions for 2 years, dose and mode of administration as prescribed by the physician

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female 18 years of age or older
Diagnosis of AAT deficiency associated emphysema
Active prescription for augmentation therapy with ARALAST
On service with Coram (a speciality pharmacy provider)
Signed and dated informed consent

Exclusion Criteria:

Clinically significant medical (other than COPD), psychiatric, or cognitive illness that, in the opinion of Coram or the sponsor or the investigator, may compromise subject safety or compliance (such as end stage renal or hepatic or heart disease, or metastatic cancer or any difficulty in communicating over the telephone lines)
Previous treatment with ARALAST (i.e. subjects who had previously received and then discontinued ARALAST augmentation therapy and are now restarting ARALAST will be excluded from the study)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313144

Locations

United States, California
Adupa Rao, MD
San Marino, California, United States, 91108

Sponsors and Collaborators

Baxter Healthcare Corporation

Investigators

Principal Investigator:

Adupa Rao, MD

Coram

More Information

No publications provided

Responsible Party:	Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT00313144 History of Changes
Other Study ID Numbers:	450501
Study First Received:	April 10, 2006
Results First Received:	March 4, 2011
Last Updated:	August 23, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema

Pathologic Processes
Alpha 1-Antitrypsin
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012