Effects of pharmacokinetic models in dosing of DDAVP and/or von Willebrand factor-containing concentrates in patients with von Willebrand disease

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2018-001631-46-NL
• Date of registration: 13/02/2019
• Prospective Registration: Yes
• Primary sponsor: Erasmus University Medical Center
• Public title: Effects of pharmacokinetic models in dosing of DDAVP and/or von Willebrand factor-containing concentrates in patients with von Willebrand disease
• Scientific title: Implementation of pharmacokinetic-guided dosing of DDAVP and VWF-containing concentrates in von Willebrand disease - OPTI-CLOT: To WiN
• Date of first enrolment: 14/02/2019
• Target sample size: 160
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001631-46
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: W. Al Arashi
• Affiliation: Erasmus University Medical Center

• Name: W. Al Arashi
• Affiliation: Erasmus University Medical Center

Key inclusion & exclusion criteria

Inclusion criteria:
- VWD and low VWF patient of all ages, with all types of VWD and “low VWF”;
- Undergoing a DDAVP-test, and/or
- Undergoing a medical intervention requiring treatment with DDAVP and/or VWF-containing concentrates with monitoring of FVIII and VWF levels. Medical interventions may include: dental, surgical or diagnostic procedures, and child deliveries in the hospital setting as examples. , or
- With bleeding requiring treatment with DDAVP and/or VWF-containing concentrate with monitoring of FVIII and VWF levels, or
- Requiring a PK profile for future medical intervention or bleeding episode, or
- With prescribed or requiring prophylaxis with VWF-containing concentrate due to bleeding frequency.

Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
- Any other known hemostatic abnormalities;
- Acquired VWD;
- Presence of VWF antibodies (>0.2 BU)
- Withdrawal of (parental) informed consent.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Von Willebrand disease
MedDRA version: 20.0 Level: LLT Classification code 10055168 Term: Von Willebrand's factor deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Minrin
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DESMOPRESSIN
CAS Number: 16679-58-6

Trade Name: Octostim
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DESMOPRESSIN
CAS Number: 16679-58-6

Trade Name: Octostim
Pharmaceutical Form: Nasal spray
INN or Proposed INN: DESMOPRESSIN
CAS Number: 16679-58-6

Trade Name: Haemate P
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: HUMAN VON WILLEBRAND FACTOR
Other descriptive name: HUMAN VON WILLEBRAND FACTOR
INN or Proposed INN: HUMAN COAGULATION FACTOR VIII
Other descriptive name: HUMAN COAGULATION FACTOR VIII

Trade Name: Wilate
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: HUMAN COAGULATION FACTOR VIII
Other descriptive name: HUMAN COAGULATION FACTOR VIII
INN or Proposed INN: HUMAN VON WILLEBRAND FACTOR
Other descriptive name: HUMAN VON WILLEBRAND FACTOR

Trade Name: Wilfactin
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: HUMAN VON WILLEBRAND FACTOR
Other descriptive name: HUMAN VON WILLEBRAND FACTOR

Trade Name: Veyvondi
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: VON WILLEBRAND FACTOR
CAS Number: 109319-16-6
Other descriptive name: VON WILLEBRAND FACTOR

Primary Outcome(s)

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: 1.
A. At least at time points t = 0 h, 1 h and 3 or 4 h after administration of DDAVP, possibly also at t = 6 h and 24 h.
B. Daily from first dose up to 14 days after surgery.
C. Daily from first or second dose up to 14 days after start of bleeding.
D. Three days for the PK-profile. During the follow up 6 times over a period of 36 months

Primary end point(s): A.In case of DDAVP-testing: predictive performance of the DDAVP population PK model: reliability of predicted FVIII and VWF:Act levels (U/ml), defined as difference between predicted and actual FVIII and VWF:Act levels (U/ml).
B.In case of elective medical interventions and treatment with DDAVP or VWF-containing concentrate: predictive performance of the Bayesian adaptive approach using the population PK model for either DDAVP or VWF-containing concentrate: reliability of predicted FVIII and VWF:Act levels (U/ml), defined as difference between predicted and actual FVIII and VWF:Act levels (U/ml) achieved after dosing according to target levels stated by consensus and treating physician.
C.In case of treatment of a bleeding episode with DDAVP or VWF-containing concentrate: predictive performance of the respective population PK models: reliability of predicted FVIII and VWF:Act levels (U/ml), defined as difference between predicted and actual FVIII and VWF:Act levels (U/ml) achieved after dosing.
D.In case of prophylaxis with VWF-containing concentrate: reliability of predicted FVIII and VWF:Act levels, defined as difference between predicted and actual FVIII and VWF:Act levels achieved after dosing (predictive performance).

Main Objective: To investigate the reliability and feasibility of PK-guided dosing of DDAVP and/or VWF-containing concentrate in VWD patients.

Secondary Outcome(s)

Secondary end point(s): 1. (Only in B & C): number and timing of DDAVP administrations and/or timing and dosing (U/kg) of VWF-containing concentrate infusions.
2. (Only in B & C): hemostasis as quantified by hemoglobin values (mmol/l), amount of blood loss (ml), incidence of thrombosis, and need for blood transfusion and/or (re)-operation.
3. (Only in B & C): duration of hospitalization (days), clinical visit (days).
4. (Only in B & C): feasibility of intervention with regard to patient and physician satisfaction and economic impact.
5. (Only in case of DDAVP-testing or DDAVP-treatment): DDAVP plasma concentrations (pg/ml).
6. (only in D): Association of (real life or simulated) FVIII and VWF:act (trough and peak levels) with bleeding episodes.

Timepoint(s) of evaluation of this end point: 1.
A. At least at time points t = 0 h, 1 h and 3 or 4 h after administration of DDAVP, possibly also at t = 6 h and 24 h.
B. Daily from first dose up to 14 days after surgery.
C. Daily from first or second dose up to 14 days after start of bleeding.
2, 3, 4. From first dose up to 14 days after surgery, or from first or second dose up to 14 days after start of bleeding.
5. At the end of treatment, or 14 days after surgery or start of bleeding.
6.
A. At least at time points t = 0 h, 1 h and 3 or 4 h after administration of DDAVP, possibly also at t = 6 h and 24 h.
B & C. Daily from first dose up to 14 days after surgery, or from first or second dose up to 14 days after start of bleeding.
D. Three days for the PK-profile. During the follow up 6 times over a period of 36 months.

Secondary ID(s)

NL65876.078.18

Source(s) of Monetary Support

Erasmus University Medical center

Ethics review

Status: Approved
Approval date: 14/02/2019
Contact: