Clinical trial NCT00524225: IL-11 in Adults With Von Willebrand Disease Undergoing Surgery
Official title: Phase II Clinical Efficacy Trial of Recombinant Interleukin-11 (rhIL-11, Neumega) in Subjects With Type 1 Von Willebrand Disease Undergoing Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Von Willebrand Disease
Keywords: IL-11
von Willebrand disease
von Willebrand factor
VWFmRNA
surgery
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2007-09-03
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Volume of Surgical Blood Loss
timeFrame: 4 weeks
measure: Volume of Blood Transfusion
timeFrame: 4 weeks
Secondary outcomes:
measure: No. of Subjects With Detectable VWFmRNA (Von Willebrand Factor Messenger RNA).
timeFrame: 4 weeks per subject
measure: Number of Subjects Who Experienced Adverse Events
timeFrame: The time frame is within 4 weeks of surgery.
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western PA
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Margaret V Ragni, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jankowitz RC, Nichols TC, Ragni MV. Recombinant IL-11 (Neumega, rhIL-11) increases plasma Von Willebrand Factor in Type 1 Von Willebrand Disease. Blood 108: 1003, 2006 (abstract).
citation: Ragni MV, Jankowitz RC, Chapman HL, Merricks EP, Kloos MT, Dillow AM, Nichols TC. A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease. Haemophilia. 2008 Sep;14(5):968-77. doi: 10.1111/j.1365-2516.2008.01827.x. Epub 2008 Aug 1.