Clinical trial NCT00000582: Cooperative Study of Factor VIII Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Blood Coagulation Disorders
Hematologic Diseases
Hemophilia A
Hemorrhagic Disorders
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 1999-10-28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To test the efficacy of prothrombin complex concentrates (Factor IX) in the treatment of hemophiliac patients who had inhibitors to Factor VIII.

Detailed description: BACKGROUND:

Despite major advances in the treatment of patients with hemophilia, a serious remaining challenge was presented by the occurrence of circulating inhibitors to Factor VIII. Because of lack of information on the natural course of patients with Factor VIII inhibitors, the relative efficacy of various modes of therapy was not established. The Division of Blood Diseases and Resources decided to sponsor a clinical investigation which would evaluate populations of hemophilia patients for Factor VIII inhibitors, follow up these patients to provide information on the natural history of the inhibitor in the hemophilia patients, and make available a reference center to monitor results and attain uniformity.

Treatment of a patient with a severe inhibitor and consequent bleeding remained a problem. Management included protracted treatment with Factor VIII, use of immunosuppressive agents and prothrombin complex (or Factor IX) concentrates. The rationale for Factor IX was that it bypassed the defect in Factor VIII caused by the inhibitor. This method of therapy attracted wide popularity, but the success was greatly debated. It was intended at the very outset of the Factor VIII study that therapeutic trials involving patients with inhibitors would not be a prime function, but that such studies would be monitored if necessary. A controlled trial of Factor IX concentrates therapy was strongly advised by the DBDR Advisory Committee. Accordingly, during fiscal year 1978, a protocol for a double-blind control study was developed by the Factor VIII inhibitor group. The trial began in the spring of 1978, and the intervention terminated about one year later.

DESIGN NARRATIVE:

Double-blind study; patients served as their own controls. A total of 51 patients each received a single large dose of Konyne, Proplex, or diluted albumin (as a control). Joint bleeding of the elbow, knee, and ankle was evaluated six hours after each dose.

Eligibility criteria: Males with hemophilia, not stratified as to ethnic group.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Louis Aledort
affiliation: University of Minnesota
name: J. Edson
affiliation: Milton S. Hershey Medical Center
name: M. Eyster
affiliation: University of Oregon Health Sciences Center
name: Scott Goodnight
affiliation: University of Colorado Medical Center
name: William Hathaway
affiliation: Milwaukee Children's Hospital
name: Jack Lazerson
affiliation: Memorial hospital
name: Peter Levine
affiliation: Wayne State University
name: Jeanne Lusher
affiliation: University of North Carolina
name: Campbell McMillan
affiliation: Thomas Jefferson University
name: Sandor Shapiro
References:
citation: Eyster ME, Gill FM, Blatt PM, Hilgartner MW, Ballard JO, Kinney TR. Central nervous system bleeding in hemophiliacs. Blood. 1978 Jun;51(6):1179-88. No abstract available.
citation: Lusher JM, McMillan CW. Severe factor VIII and factor IX deficiency in females. Am J Med. 1978 Oct;65(4):637-48. doi: 10.1016/0002-9343(78)90852-5.
citation: Kasper CK. Effect of prothrombin complex concentrates on factor VIII inhibitor levels. Blood. 1979 Dec;54(6):1358-68.
citation: Lusher JM, Shapiro SS, Palascak JE, Rao AV, Levine PH, Blatt PM. Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: a multicenter therapeutic trial. N Engl J Med. 1980 Aug 21;303(8):421-5. doi: 10.1056/NEJM198008213030803.
citation: Gerety RJ, Eyster ME, Tabor E, Drucker JA, Lusch CJ, Prager D, Rice SA, Bowman HS. Hepatitis B virus, hepatitis A virus and persistently elevated aminotransferases in hemophiliacs. J Med Virol. 1980;6(2):111-8. doi: 10.1002/jmv.1890060203.