VA Cooperative Study of the Efficacy of Hepatitis Immune Serum Globulin for the Prevention or Modification of Post-Transfusion Hepatitis (VA2-TAH) - Catalog

Name

VA Cooperative Study of the Efficacy of Hepatitis Immune Serum Globulin for the Prevention or Modification of Post-Transfusion Hepatitis (VA2-TAH)

Accession Number

HLB01031313a

Acronym

VA2-TAH

Related studies

(NANB-TAH) Natural History Study of Non-A, Non-B Post-Transfusion Hepatitis (NANB-TAH)

BSI Study IDs

PTS

Is public use dataset

False

Keywords

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

False

Clinical Trial URLs
N/A
Study type

Clinical Trial

Collection Type

Open BioLINCC Study

Cohort type

Adult

Interventions

Study Open Date (Data)

2013-06-21

Study Open Date (Specimens)

2013-06-21

Date materials available

2013-06-20

Last updated

2023-02-07

Study period

1972 – 1976

Study Contacts
NHLBI Division

DBDR

Classification

Transfusion Medicine

HIV study classification

non-HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

0

# of Returned Specimens

0

Primary Publication URLs
N/A
Conditions

Blood Transfusion
Hepatitis, Viral, Human

Objectives

This double blind, randomized, controlled trial was designed to test the efficacy of hepatitis B immune serum globulin (HBIG) for the prevention or modification of post-transfusion hepatitis (PTH).

Background

In the mid-1960’s, PTH was a major health problem in the US. Approximately 30,000 cases occurred each year, resulting in 1,500 to 3,000 deaths annually. The incidence of HBs Ag-associated hepatitis declined dramatically after 1973 with the institution of routine screening of donor blood by radioimmunoassay techniques, although no change in the incidence of antigen-negative hepatitis had occurred. An earlier randomized, double-blind clinical trial had been conducted in 11 Veterans Administration (VA) hospitals between 1969 and 1973 to evaluate the efficacy of immune serum globulin (ISG) in comparison to placebo as prophylaxis against post-transfusion hepatitis. The results indicated that ISG prohibited the development of PTH in specific circumstances. ISG led to a significant decrease in the incidence of icteric type non-B hepatitis among patients who had been transfused with three or more units of commercial blood, but had little effect on the hepatitis that developed among those that received volunteer donor blood (1). Since hepatitis B represented 22% of cases of PTH, a second randomized study was undertaken immediately on conclusion of the first one to compare the efficacy of ISG with HBIG.

Subjects

A total of 986 patients were enrolled between 1973 and 1975 at 6 Veterans Administration hospitals. A subset of this cohort was subsequently recruited into the Natural History Study of Non-A, Non-B Post Transfusion Hepatitis (NANB-TAH) that also has data and biospecimens available. The VA2-TAH cohort can be longitudinally linked to the NANB-TAH study data.

Design

Eighteen of the enrolled subjects had tested positive for pre-existing Hepatitis B surface antigen (HBsAg). They were not randomized and were given ISG. Of the remainder, 482 were randomized to ISG and 486 to HBIG. Patients were eligible for the trial if they received one or more transfusions of whole blood or packed cells, did not meet any of the exclusion criteria, and could be randomized and receive their first injection within 120 hours of the first transfusion. Exclusion criteria included the likelihood of repeated transfusions in the next six months, transfusions or gamma globulin products within the previous six months, serious illnesses limiting survival, previous participation in this trial, and unwillingness to sign the informed consent. Patients were randomized and received their first injection within 120 hours of transfusion. They were then followed at two-week intervals for six months and then at weeks 35, 44, and 52. Patients with alanine aminotransferase value of >40 Karmen Units (KU) were also tested for bilirubin, aspartate aminotransferase and alkaline phosphatase and followed at weekly intervals for a minimum of four weeks (intensive visits). The diagnosis of hepatitis was made using a scoring algorithm (Protocol Appendix I).


Pre-transfusion and donor blood samples were obtained from the Blood Bank. All blood samples were tested for HBsAg and antibody to HBsAg (anti-HBs). All donor blood was pre-screened for HBsAg and when possible retested for HBsAg and anti-HBs. Hepatitis B was defined as the development of HBsAg or anti-HBs in patients that met the definition of acute hepatitis. Selected samples were also tested for anti-HBs and for the antibody to Hepatitis B core antigen (HBc).

Conclusions

PTH was diagnosed in 11.0% of the HBIG group (53/482) compared to 14.2% of the ISG group (69/486), p = 0.13 (2,3). Hepatitis B developed in 4 of 969 patients that received ISG or HBIG although all donor blood was screened and found to be HBsAg–negative by radioimmunoassay. Subsequent testing of recipient and donor blood samples for anti-HBc demonstrated the importance of anti-HBc as an indicator of hepatitis B infection and supported the hypothesis that high-titer anti-HBc positive blood is infectious (4).

Disease classification

Publications

Mat types

Serum

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    Not Randomized, HBSAG+, Received IG: 18

    Immune serum globulin: 482

    Hepatitis B immune serum globulin: 486


    Last Modified: July 28, 2014, 3:08 p.m.
  • Age
     

    Not Randomized,

    HBSAg+,

    received IG

    Immune

    serum

    globulin

    Hepatitis B

    immune serum

    globulin

    All

    N

    %

    N

    %

    N

    %

    N

    %

    16-20

    .

    .

    .

    .

    4

    0.82

    4

    0.41

    21-25

    .

    .

    10

    2.07

    12

    2.47

    22

    2.23

    26-30

    .

    .

    15

    3.11

    11

    2.26

    26

    2.64

    31-35

    1

    5.56

    10

    2.07

    6

    1.23

    17

    1.72

    36-40

    1

    5.56

    13

    2.70

    22

    4.53

    36

    3.65

    41-45

    1

    5.56

    43

    8.92

    45

    9.26

    89

    9.03

    46-50

    5

    27.78

    91

    18.88

    73

    15.02

    169

    17.14

    51-55

    7

    38.89

    121

    25.10

    130

    26.75

    258

    26.17

    56-60

    3

    16.67

    84

    17.43

    84

    17.28

    171

    17.34

    61-65

    .

    .

    50

    10.37

    55

    11.32

    105

    10.65

    66-70

    .

    .

    23

    4.77

    25

    5.14

    48

    4.87

    71-75

    .

    .

    10

    2.07

    10

    2.06

    20

    2.03

    76-80

    .

    .

    10

    2.07

    8

    1.65

    18

    1.83

    81-85

    .

    .

    2

    0.41

    1

    0.21

    3

    0.30

     

    Last Modified: March 11, 2016, 2:48 p.m.
  • Sex

     

    Not Randomized,

    HBSAg+,

    received IG

    Immune

    serum

    globulin

    Hepatitis B

    immune serum

    globulin

    All

    N

    %

    N

    %

    N

    %

    N

    %

    Female

    .

    .

    7

    1.45

    8

    1.65

    15

    1.52

    Male

    18

    100.00

    475

    98.55

    478

    98.35

    971

    98.48

     

    Last Modified: March 11, 2016, 2:48 p.m.
  • Race

     

    Not Randomized,

    HBSAg+,

    received IG

    Immune

    serum

    globulin

    Hepatitis B

    immune serum

    globulin

    All

    N

    %

    N

    %

    N

    %

    N

    %

    White

    9

    50.00

    375

    77.80

    383

    78.81

    767

    77.79

    Black

    9

    50.00

    104

    21.58

    97

    19.96

    210

    21.30

    Other

    .

    .

    3

    0.62

    6

    1.23

    9

    0.91

     

    Last Modified: March 11, 2016, 2:48 p.m.

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

  • Material Types

    Last Modified: Nov. 30, 2015, 4:04 p.m.
  • General Freeze/Thaw Status
  • Visits (Vials)

    02/26/2018

      Serum Total
    1 Visit per Subject 18 18
    2 Visits per Subject 47 47
    3 Visits per Subject 48 48
    4 Visits per Subject 100 100
    5 Visits per Subject 84 84
    6-10 Visits per Subject 1,377 1,377
    11-20 Visits per Subject 11,311 11,311
    21+ Visits per Subject 1,477 1,477
    No Visit Date 1,846 1,846
    Donor Sample 4,148 4,148
     

    Last Modified: Feb. 26, 2018, 2:52 p.m.
  • Visits (Subjects)

    02/26/2018

      Serum
    Total number of subjects Average volume (ml) per subject
    1 Visit per Subject 17 1.90
    2 Visits per Subject 21 3.56
    3 Visits per Subject 16 4.96
    4 Visits per Subject 25 7.41
    5 Visits per Subject 14 10.28
    6-10 Visits per Subject 142 17.27
    11-20 Visits per Subject 670 33.27
    21+ Visits per Subject 51 53.53
    No Visit Date 906 3.01
    Donor Sample 893 4.04
     

    Last Modified: Feb. 26, 2018, 2:52 p.m.