Study of Pharmacokinetic-guided dosing of clottiing factor in Hemophilia.

• Register: EUCTR
• Last refreshed on: 9 November 2020
• Main ID: EUCTR2013-000909-24-NL
• Date of registration: 24/05/2013
• Prospective Registration: Yes
• Primary sponsor: Erasmus MC
• Public title: Study of Pharmacokinetic-guided dosing of clottiing factor in Hemophilia.
• Scientific title: "OPTI-CLOT": Peri-Operative PharmacokineTIc-guided dosing of CLOTting factor in Hemophilia. - OPTICLOT
• Date of first enrolment: 29/08/2013
• Target sample size: 72
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000909-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: implementation of a trainings cohort of n=7. If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: PK guided dosing arm vs standard treatment arm Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: I. van Vliet
• Affiliation: Erasmus MC

• Name: I. van Vliet
• Affiliation: Erasmus MC

Key inclusion & exclusion criteria

Inclusion criteria:
- Severe and moderate hemophilia A or B (FVIII/FIX plasma level = 5%)
- Elective and low or medium risk surgery as defined by surgical risk score (form B)
- = 12 years of age at inclusion date for the randomized controlled trial;
- < 12 years of age at inclusion date for the PK-guided dosing observational children cohort.
- Written informed consent.

Are the trial subjects under 18? yes
Number of subjects for this age range: 72
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Patients with other congenital or acquired hemostatic abnormalities.
- Withdrawal of (parental) informed consent.
- Detectable FVIII/FIX inhibiting antibodies (>0.02 BU) at inclusion in study.
- General medical conditions which may interfere with participation in the study.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Hemophillia
MedDRA version: 20.0 Level: LLT Classification code 10066439 Term: Hemophilia System Organ Class: 100000004850
MedDRA version: 20.0 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850
MedDRA version: 20.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850

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

Intervention(s)

Trade Name: Advate
Pharmaceutical Form: Powder and solvent for solution for injection

Trade Name: Kogenate
Pharmaceutical Form: Powder and solvent for solution for injection

Trade Name: Helixate NexGen
Pharmaceutical Form: Powder and solvent for solution for injection

Trade Name: Refacto
Pharmaceutical Form: Powder and solvent for solution for injection

Trade Name: Benefix
Pharmaceutical Form: Powder and solvent for solution for injection

Trade Name: Aafact
Pharmaceutical Form: Powder and solution for solution for injection

Trade Name: NovoEight
Pharmaceutical Form:

Primary Outcome(s)

Primary end point(s): 1. Amount of infused FVIII/FIX concentrate per kilogram during peri-operative period per postoperative day (0-14 days after day of surgery).

Timepoint(s) of evaluation of this end point: After 14 days

Secondary Objective: 1. Peri-operative hemostasis as quantified by hemoglobin values pre- and postoperative, blood loss and classification of expected blood loss during surgical procedure as documented by standardized form.
2. Achieved FVIII/FIX levels after recombinant FVIII/FIX infusion (IU ml-1)
3. Length of hospitalization (days).
4. Effect of baseline VWF antigen, propeptide values and blood type on FVIII/FIX clearance.
5. Economic evaluation.

Main Objective: 1. To investigate whether peri-operative dosing using a population-based pharmacokinetic model (non-linear mixed effect modelling) in hemophilia patients leads to a significant reduction in clotting factor consumption in comparison to the standard dosing procedure, without an increase in bleeding risk.

Secondary Outcome(s)

Secondary end point(s): 1. Peri-operative hemostasis quantified by standardized form (form A).
2. Achieved FVIII/FIX levels (IU ml-1) after recombinant FVIII/FIX infusion.
3. Duration of hospitalization(day of release – day of surgery/ start of continuous or bolus FVIII/FIX infusion).
4. Effect of baseline VWF antigen, propeptide values and blood type on FVIII/FIX clearance.
5. Economic analysis of costs in both treatment arms, differentiation between bolus and continuous infusion.

Timepoint(s) of evaluation of this end point: Within 6 months of last patient last visit

Secondary ID(s)

201302-OPTICLOT

4121

Source(s) of Monetary Support

ZON-MW

Ethics review

Status: Approved
Approval date: 29/08/2013
Contact: