Study of Heparin Prophylaxis of Hereditary Angioedema Exacerbations
Study of Heparin Prophylaxis of Hereditary Angioedema Exacerbations
OBJECTIVES:

 I. Determine the safety and efficacy of inhaled and subcutaneously administered heparin in
 the treatment of hereditary angioedema.
PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, 3 way crossover
 study.

 All patients complete diary cards for the first month of the study in order to determine
 compliance in providing a daily record of symptoms and medication taken. All compliant
 patients receive subcutaneously injected heparin twice daily, inhaled heparin daily, or
 matched saline placebo in a random order. Each of the three drug administration periods lasts
 2 months, for a total of 6 months of treatment. Patients who have a flare in disease activity
 that requires hospitalization are terminated from that drug administration period of the
 study.

 Patients are followed biweekly during the first month and again at the end of the second
 month for each of the three 2 month drug administration periods.

 Completion date provided represents the completion date of the grant per OOPD records
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 -  Confirmed diagnosis of hereditary angioedema (HAE) based upon C4 antigenic level,
 positive family history, and C1 inhibitor (C1INH) antigenic level (Type I HAE) or
 functional level (Type II HAE)

 -  Functional C1 within normal levels if diagnosis of acquired C1INH is possible

 -  Negative family history will not exclude as long as patient meets all other criteria,
 has normal C1 level, and has no evidence of acquired C1INH deficiency

 -  History of symptoms of HAE including episodic swelling, abdominal pain, and/or
 respiratory difficulty

 -  Experiencing a minimum of 1-2 HAE episodes within 6 weeks

 --Prior/Concurrent Therapy--

 -  Endocrine therapy: Anabolic steroids allowed as long as dose has not been changed in
 at least 30 days

 -  Other: No concurrent and at least 1 week since prior aspirin, nonsteroidal
 antiinflammatory agents, dipyridamole, Coumadin-like drugs, or any other medication
 having an effect on coagulation or platelets

 --Patient Characteristics--

 -  Hematopoietic: No clinically significant history of hematologic disease

 -  Hepatic: No clinically significant history of hepatic disease

 -  Renal: No clinically significant history of renal disease

 -  Cardiovascular: No clinically significant history of cardiac disease or hypertension

 -  Pulmonary: No clinically significant history of pulmonary disease

 -  Other: No contraindication to the use of inhaled or subcutaneous heparin No drug
 allergy that would interfere with the study No clinically significant history of:
 Malignancy Diabetes mellitus Neurologic disease Immunologic disease Bleeding disorder
 Infirmity No history of drug abuse, alcoholism, psychosis, or other
 psychological/psychiatric disorder