A randomised, open-label, multi-centre trial investigating the intra-subject variability of ROTEM® and TEG® parameters following two intravenous administrations of the same dose of activated recombinant factor VII (rFVIIa/NovoSeven®) in haemophilia patients in a non-bleeding state

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-000891-42-DK
• Date of registration: 08/07/2005
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A randomised, open-label, multi-centre trial investigating the intra-subject variability of ROTEM® and TEG® parameters following two intravenous administrations of the same dose of activated recombinant factor VII (rFVIIa/NovoSeven®) in haemophilia patients in a non-bleeding state
• Scientific title: A randomised, open-label, multi-centre trial investigating the intra-subject variability of ROTEM® and TEG® parameters following two intravenous administrations of the same dose of activated recombinant factor VII (rFVIIa/NovoSeven®) in haemophilia patients in a non-bleeding state
• Date of first enrolment: 07/09/2005
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000891-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes 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

Countries of recruitment

Denmark

Key inclusion & exclusion criteria

Inclusion criteria:
• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the patient.)
• Confirmed diagnosis of congenital haemophilia A or B with a FVIII:C or FIX:C one stage activity, respectively, at less than 5% of normal (based on medical records) +/- inhibitors (a positive inhibitor status defined as >0.6 Bethesda units)
• Male subjects, 16 years of age or more
• Non-bleeding state (i.e. no clinical manifestation of active bleed) at the time of administration of trial product

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

Exclusion criteria:
• Known or suspected allergy to trial product or any of its components or to related products
• Previous participation in this trial defined as randomisation of the patient
• Known clinically relevant coagulation disorders or insufficiencies other than congenital haemophilia A or B
• Platelet count < 50,000 platelets/µL
• Received any haemostatic treatment (e.g. Feiba) within the last 7 days prior to administration of trial product, except for rFVIIa
• Received rFVIIa within the last 48 hours prior to administration of trial product
• Participation in any other trial involving investigational products within the last 30 days prior to administration of trial product
• Received immunosuppressive-immunomodulatory drugs within the last 30 days prior to administration of trial product
• Advanced atherosclerotic disease, incl. any history of thrombotic disorder (myocardial infarction, deep vein thrombosis, pulmonary embolism, stroke or peripheral arterial thrombosis)
• Septicaemia, e.g. febrile illness within 5 days prior to trial product administration
• Renal insufficiency defined as current dialysis therapy or creatinine levels above normal range (according to local laboratory range)
• Hepatic disease
? Patients with significant hepatic enzyme elevation (ALAT x 2 upper reference limit and/or PT<70%)
? Known current hepatic dysfunction or severe hepatic disease during the last 12 months.
• Any disease or condition which, according to the Investigator´s judgement, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation


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

Health Condition(s) or Problem(s) studied

Haemophilia
MedDRA version: 7.1 Level: LLT Classification code 10061992

Intervention(s)

Trade Name: NovoSeven
Product Name: NovoSeven®
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: eptacog alfa (activated)
CAS Number: 102786-61-8
Other descriptive name: Blood-coagulation factor VIIa; Human recombinant coagulation factor VIIa
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.6-

Primary Outcome(s)

Primary end point(s): Primary endpoints
• TEG® parameters (R time, K time, a, MA and LY30) prior to and at 15, 60, 120, 240 minutes after dosing of rFVIIa
• ROTEM® parameters (CT, CFT, a, MCT and LI60) prior to and at 15, 60, 120, 240 minutes after dosing of rFVIIa

Secondary endpoints
• TEG® parameters (R time, K time, a, MA and LY30) obtained from blood samples spiked ex-vivo with rFVIIa (corresponding to 45, 90 and 180 µg/kg)
• ROTEM® parameters (CT, CFT, a, MCT and LI60) obtained from blood samples spiked ex-vivo with rFVIIa (corresponding to 45, 90 and 180 µg/kg)
• FVIIa:C, FX:C, fibrinogen, number of platelets and total platelet volume, PT and aPTT prior to and at 15, 60, 120, 240 minutes after dosing of rFVIIa
• Serious adverse events regardless of causality and non-serious adverse events judged by the Investigator to be related to trial product administration

Secondary Objective: • To evaluate whether there is a correlation between different doses of rFVIIa and the ROTEM® and TEG® parameters
• To evaluate whether there is a correlation between thromboelastographic parameters as determined by ROTEM® and by TEG®
• To compare the in vivo reproducibility of thromboelastographic parameters as determined by ROTEM® and by TEG®
• To evaluate the inter-subject variability of thromboelastographic parameters as measured by ROTEM® and by TEG®
• To evaluate whether there is a correlation between the response of in vivo and ex vivo supplementation of rFVIIa
• To evaluate whether there is a correlation between the in vivo ROTEM® or TEG® parameters and the following parameters FVIIa:C, FX:C, Fibrinogen, Number of platelets and total platelet volume, PT and aPTT
• To evaluate the safety of rFVIIa administration

Main Objective: • To evaluate the intra-subject variability (in vivo reproducibility) of thromboelastographic parameters as measured by ROTEM® and by TEG® prior to and at 15, 60, 120 and 240 minutes following two administrations of the same dose of activated recombinant human FVII (rFVIIa) in haemophilia patients in a non bleeding state

Secondary ID(s)

NN1731-1668