Clinical trial NCT02453542: Global Haemostatic Methods Following Administration of Bypassing Agents to Patients With Haemophilia With Inhibitors
Official title: Global Haemostatic Methods to Measure the Treatment Effect Following Administration of Bypassing Agents to Patients With Haemophilia With Inhibitors
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hemophilia
Keywords: hemophilia
inhibitors
thrombin
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2015-05-25
Enrollment: 20
Sex: MALE
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Fifteen patients (adults and children) with hereditary haemophilia with inhibitors.

Five patients (adults) with acquired haemophilia

Brief summary: Background

The treatment of haemophilia A and B has been revolutionized by the use of factor concentrate, both as prophylaxis and to treat bleeding episodes (on-demand treatment). However, despite its advantages, repeated treatment with factor concentrate can lead to development of inhibitors (antibodies) towards the coagulation factor in the concentrate. Another patient group in which the bleeding symptoms are difficult to treat because of inhibitors towards coagulation factors, most commonly FVIII, is patients with acquired haemophilia. Patients with high antibody titers exhibit a deficient or no response to factor concentrates and usually need treatment with bypassing agents, namely factor eight inhibitor bypassing agent (FEIBA®, Baxter) och recombinant activated factor VII (rFVIIa, Novo-Seven®, Novo Nordisk). The effect of the treatment cannot be accurately monitored by traditional coagulation tests.

The aim of the study is to evaluate the utility of the global haemostatic methods in patients with haemophilia with inhibitors. The objective is to improve the monitoring of the treatment effect and thus increase the safety of the patient and the effectiveness of the treatment.

Patients and methods

Patients

The primary cohort will consist of fifteen patients with inherited haemophilia with inhibitors as well as five adult patients with acquired haemophilia who are followed up at the Coagulation Department of the Karolinska University Hospital, Stockholm, Sweden.

Blood samples will be collected from those patients at specific time points (see Design of the study) during the course of two years (for each patient). The treatment (type, dose, duration) will be determined by the treating physician.

Methods (selection)

* Thrombin generation (Calibrated Automated Thrombogram, CAT® and a commercial kit from Siemens®).
* Overall haemostatic potential (OHP)

Design of the study

Timeframe for blood sampling: i) baseline (inclusion in the study), and ii) prior and after administration of bypassing agents to either treat bleeding symptoms or before an invasive procedure or as prophylaxis.

Data analysis

The variations in coagulation markers measured as described above (Methods) will be associated to the clinical symptoms (bleeding), the level of coagulation factors (if measurable) and the titers of the inhibitors.


Eligibility criteria: Inclusion Criteria:

* informed consent
* meets the study population description

Exclusion Criteria:

* no informed consent age\<7 years

Primary outcomes:
measure: Changes in coagulation markers, such as thrombin generation markers (Endogenous Thrombin Potential in nano molar thrombin*minute and peak thrombin in nano molar and fibrin aggregation curves, following administration of bypassing agents.) composite
timeFrame: participants will be followed up for up to 2 years following inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Solna
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Karolinska Institutet
name: Roza Chaireti, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: