IL-11 in Adults With Von Willebrand Disease Undergoing Surgery

Phase 2

Terminated

Brief Summary: The purpose of this study is to determine the efficacy and safety of rhIL-11 when given subcutaneously in adults with type 1 von Willebrand disease undergoing elective surgery or major dental procedure. Efficacy will be measured by estimated blood loss, and frequency and severity of bleeding and transfusion requirement during and after surgery. Safety will be measured by the frequency of adverse events, including fever, headache, fatigue, myalgias, arthralgias, fluid retention, or edema.

Detailed Description: This study is a prospective, single-center Phase II trial of Neumega (rhIL-11) in adults with type 1 VWD undergoing elective surgery or major dental procedure. It is anticipated that 10 subjects who meet eligibility criteria will enroll and complete the study. The specific objectives are to determine the efficacy and safety or rhIL-11 during and after elective surgery, and to determine the mechanism of the hemostatic response of rhIL-11.

Recruitment & Eligibility

Inclusion Criteria

Males and females 18 years of age and older
Confirmed type 1 VWD, as defined by low VWF:RCoF or low VWF:Ag and qualitatively normal VWF multimers
A past bleeding history
Responsive to DDAVP
Scheduled elective major surgery or major dental surgery at MUH or PUH
Willingness to have blood drawn

Exclusion Criteria

Presence of other bleeding disorders, acquired Von Willebrand disease, primary thrombocytopenia
Use of immunomodulatory or experimental drugs, or diuretics
Pregnant or lactating women or those unwilling to use contraception during study
Previous cardiac disease, congestive failure, arrhythmia (e.g. atrial fibrillation, atrial flutter), hypertension, MI, stroke, or thrombosis
Past allergic reaction to Neumega or DDAVP
Surgery within the past 8 weeks
Inability to comply with study protocol requirements
Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs
Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing substantial quantities of FVIII and/or VWF within five days of study
Past allergic reaction to Neumega or DDAVP
Surgery within the past 8 weeks
Inability to comply with study protocol requirements
Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs
Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing substantial quantities of FVIII and/or VWF within five days of study

Arm && Interventions

Group	Intervention	Description
Neumega (Interleukin 11, IL-11)	Neumega (Oprelvekin, Interleukin 11, IL-11)	Neumega (Oprelvekin, Interleukin 11, IL-11) 25 mcg/kg subcutaneously, given for 4 days preoperatively, and on day 5 preoperatively, and for up to 2 days postoperatively

Primary Outcome Measures

Name	Time	Method
Volume of Surgical Blood Loss	4 weeks	Hemostatic efficacy was measured by estimated blood loss (cc) during the surgical procedure.
Volume of Blood Transfusion	4 weeks	The volume of blood transfusion required (units of blood) after the surgical procedure.

Secondary Outcome Measures

Name	Time	Method
No. of Subjects With Detectable VWFmRNA (Von Willebrand Factor Messenger RNA).	4 weeks per subject	The number of subjects with detectable VWFmRNA.
Number of Subjects Who Experienced Adverse Events	The time frame is within 4 weeks of surgery.	mild headache, nausea