Condition category
Circulatory System
Date applied
04/09/2008
Date assigned
13/10/2008
Last edited
13/10/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Pierre Coriat

ORCID ID

Contact details

Groupe Hospitalier Pitié Salpêtrière
Departement d'Anesthésie
Boulevard de l'hôpital 47-83
F-75651 Paris cedex 13
Paris
F-75651
France

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

LEX-206

Study information

Scientific title

Efficacy and safety of two dose regimens of Octaplex® in patients with intracranial haemorrhage related to oral anticoagulant therapy: a multicentre, prospective, randomised, open-label study

Acronym

Study hypothesis

To compare the efficacy of two dose regimens of Octaplex® on the international normalised ratio (INR) at 10 ± 5 minutes after the end of injection in patients with intracranial haemorrhage related to oral anticoagulant therapy.

Ethics approval

Ethics approval received from the Ouest III Ethics Committee (Poitiers, France) on the 7th February 2008 (ref: 08.01.01)

Study design

Interventional, prospective, multicentre, randomised, open-label, phase III, parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Intracranial haemorrhage (intracerebral and acute subdural haematoma)

Intervention

Octaplex® intravenous administration at the inclusion, 25 IU/kg or 40 IU/kg according to the randomisation. In addition, administration of 5 mg vitamin K, intravenous infusion for all the patients.

Possibility of two more administrations upon INR results:
1. A rescue dose at 10 ± 5 minutes after the first administration if INR not corrected (INR greater than 1.5), intravenous administration within 10 minutes, dose administrated = theoretical dose calculated according to the Summary of Product Characteristics (SmPC) - dose administrated at the inclusion (25 or 40 IU/kg)
2. New dose at 6 hours if INR greater than 2, dose calculated according the SMPc, intravenous administration within 10 minutes

Comparison of two doses of Octaplex®, no placebo or other treatment used. Patients will be followed up during 30 days or less if discharged.

Intervention type

Drug

Phase

Phase III

Drug names

Octaplex®

Primary outcome measures

INR at 10 ± 5 minutes after the end of injection in patients with intracranial haemorrhage related to oral anticoagulant therapy, measured by local laboratories (standard method).

Secondary outcome measures

Efficacy:
1. Laboratory parameters (coagulation): INR, prothrombin time (PT), thrombin generation assay (TGA), coagulation factors II, VII, IX and X, protein C and protein S at 10 ± 5 minutes, 1, 3, 6 and 24 hours after the end of injection. All these parameters will be analysed by local or central laboratory using standard methods.
2. Medical imaging (CT scan): volume of haematoma at 48 hours after the end of injection (or earlier in case of neurological worsening assessed by National Institutes of Health [NIH] Stroke Scale); the computed tomography images at T0 and T48 hours will be analysed by the central neuroradiology centre with the software OSIRIX
3. Clinical status: Glasgow Coma Scale (score: 3 - 15) and NIH Stroke Scale at 1, 24 and 48 hours, and on days 3 and 30 (or earlier if patient discharged) after the end of injection
4. Global outcome:
4.1. Survival (is the patient dead? Yes or No)
4.2. Extended Glasgow Outcome Scale (GOS) (score: 1 - 8, 1 = dead, 8 = upper good recovery)
4.3. Modified Rankin Scale (MRS) (score: 0 - 6, 0 = no symtoms at all, 6 = dead)
4.4. Barthel Index (score: 0 - 100, 100 = patient is continent, feeds himself, dresses himself, gets up out of bed and chairs, bathes himself, walks at least a block, and can ascend and descend stairs)
All measured on day 30 (or earlier if patient discharged) after the end of injection.
5. Overall clinical response: this assessment will be done by the investigator using a verbal rating scale:
5.1. None: in spite of sufficient treatment uncontrolled intracranial bleeding growth requiring additional measures
5.2. Moderate: in spite of sufficient treatment uncontrolled intracranial bleeding and haematoma growth; no additional measures required
5.3. Excellent: intracranial bleeding and haematoma growth under control, comparable to a normal patient
Measured 48 hours after the end of injection.

Safety:
6. Study drug actually received
7. Adverse events (AEs) during the whole stay in all patients. AEs will be followed closely by a Data Monitoring Committee (DMC) whose assignment will be to identify possible thromboembolic complications. The DMC will be entitled to issue recommendations to the sponsor and the investigators regarding the continuation or the modification of the study if there is a suspicion of increased risk of thromboembolic complications in the high dose group.
8. Vital signs: continuous monitoring of arterial blood pressure, heart rate, respiratory rate and body temperature during the whole stay in the investigator's ward; recording of values and abnormalities at 10 ± 5 minutes, 1, 6, 24 and 48 hours and on days 3 and 30 (or earlier if patient discharged) after the end of injection
9. Electrocardiogram (ECG): continuous surveillance during the whole stay in the investigator's ward; recording of abnormalities at 10 ± 5 minutes, 1, 3, 6, 24 and 48 hours and on days 3 and 30 (or earlier if patient discharged) after the end of injection
10. Laboratory parameters (coagulation markers): D-dimers, prothrombin fragments F1+2 at 10 ± 5 minutes, 1, 3, 6 and 24 hours after the end of injection
11. Other laboratory parameters: troponins, electrolytes, urea, creatinine, liver function and haematology at 24 hours after the end of injection
12. Digital glucose at 24 hours after the end of injection

Quality of life measurements:
13. Pharmaco-economic patient questionnaire at month 3
14. 36-item short form health survey (SF-36) questionnaire at month 3

Overall trial start date

10/09/2008

Overall trial end date

31/03/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients of 18 years of age or older, either sex
2. Intracranial haemorrhage (intracerebral and acute subdural) confirmed by medical imaging (computed tomography only)
3. Use of oral anticoagulant, only vitamin K antagonist
4. Written informed consent from the patient or a legally acceptable representative if the subject is unable to provide informed consent, or from the investigator and an independent witness from the investigator and the sponsor, if no legally acceptable representative is available at inclusion

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60 (2 x 30 patients)

Participant exclusion criteria

1. Deep coma on admission (score 3 to 5 on the Glasgow Coma Scale) because their probability of survival is close to zero
2. Septic shock or severe sepsis in the past fourteen days prior to inclusion
3. Crush injury in the past seven days prior to inclusion
4. Known or suspected disseminated intravascular coagulation
5. Pulmonary embolism or phlebitis in the last 3 months prior to inclusion
6. Patients receiving vitamin K prior to admission to investigational centre
7. Known allergy to vitamin K or to any of its excipients
8. Hypersensitivity to the active substances of Octaplex® (human coagulation factors II, VII, IX and X) or to any of its excipients (heparin and sodium citrate)
9. Known allergy to heparin or history of heparin-induced thrombocytopenia
10. Participation in another clinical study, currently or during the past three months
11. Pregnant or lactating women
12. Jehovah's witnesses

Recruitment start date

10/09/2008

Recruitment end date

31/03/2009

Locations

Countries of recruitment

France

Trial participating centre

Groupe Hospitalier Pitié Salpêtrière
Paris
F-75651
France

Sponsor information

Organisation

Octapharma AG (Switzerland)

Sponsor details

Seidenstrasse 2
Lachen
CH-8853
Switzerland

Sponsor type

Industry

Website

http://www.octapharma.com

Funders

Funder type

Industry

Funder name

Octapharma AG (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes