Von Willebrand Disease
Conditions
Keywords
IL-11, von Willebrand disease, von Willebrand factor, VWFmRNA, surgery
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.
Interventions
25 micrograms/kg by subcutaneous injection once daily for four days, followed by once daily on days 1-3 before and after elective surgery or dental procedure
Sponsors
University of North Carolina
Wyeth is now a wholly owned subsidiary of Pfizer
Margaret Ragni
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neumega (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
Neumega (Oprelvekin, Interleukin 11, IL-11): 25 micrograms/kg by subcutaneous injection once daily for four days, followed by once daily on days 1-3 before and after elective surgery or dental procedure | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Neumega (Interleukin 11, IL-11) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Volume of Blood Transfusion
The volume of blood transfusion required (units of blood) after the surgical procedure.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neumega (Interleukin 11, IL-11) | Volume of Blood Transfusion | NA units of blood |
Primary
Volume of Surgical Blood Loss
Hemostatic efficacy was measured by estimated blood loss (cc) during the surgical procedure.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neumega (Interleukin 11, IL-11) | Volume of Surgical Blood Loss | NA cc |
Secondary
No. of Subjects With Detectable VWFmRNA (Von Willebrand Factor Messenger RNA).
The number of subjects with detectable VWFmRNA.
Time frame: 4 weeks per subject
Population: Even though three subjects were enrolled, none were assessed for VWFmRNA because the study stopped due to poor enrollment related to insurers requiring surgeries outside of UPMC.
Secondary
Number of Subjects Who Experienced Adverse Events
mild headache, nausea
Time frame: The time frame is within 4 weeks of surgery.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neumega (Interleukin 11, IL-11) | Number of Subjects Who Experienced Adverse Events | Mild headache | 1 participants |
| Neumega (Interleukin 11, IL-11) | Number of Subjects Who Experienced Adverse Events | nausea | 1 participants |