Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens

NCT ID: NCT02314325

Last Updated: 2014-12-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-10-31

Brief Summary

This trial is designed to assess if there is evidence of subclinical joint bleeding on MRI/X-Ray in adults with severe Haemophilia A while on standard and/or pharmacokinetically tailored prophylaxis regimens. Participants with severe Haemophilia A will have longitudinal MRI and XRay imaging of their elbows, ankles and knees at 0, 6 and 18 months while on standard ( 0-6 months) and then pharmacokinetically tailored (7-18 months) recombinant Factor VIII prophylaxis.

Detailed Description

Subclinical joint bleeding (SJB) in Haemophilia may cause early and progressive joint damage. Clinical haemarthrosis is a traditional outcome measure in Haemophilia trials but may not always correlate with the degree of arthropathy. Even in the absence of haemarthrosis, abnormalities may be detected on MRI. MRI offers greater sensitivity than physical examination for early joint damage and use of the International Prophylaxis Study Group (IPSG) score allows standardisation across clinical trials. Early awareness of haemophiliac arthropathy can prompt intervention with physiotherapy, specific exercise programmes, optimization of prophylaxis and orthotics to improve overall joint outcomes.

The time spent with Factor VIII (FVIII) levels <0.01 IU/mL is a known risk for bleeding. Conventional prophylaxis schedules follow a weight based regimen and are titrated according to clinical bleeds. FVIII pharmacokinetics (PK) may be used to optimise FVIII prophylactic regimens, maintaining adequate FVIII trough levels. This offers the possibility to not only tailor individual regimens but also may potentially reduce the rate of clinical and subclinical joint bleeding.

This is a national, investigator led clinical trial investigating the feasibility of PK tailored prophylaxis in adults with severe Haemophilia A. This trial will prospectively and longitudinally assess SJB and joint health in Irish adults with severe Haemophilia A.

SJB will be compared while on standard (weight based, 20-40 IU/kg) and PK tailored prophylaxis(maintaining trough FVIII > 0.015 IU/mL). This is a crossover study will participants spending months 0-6 on standard prophylaxis and then changing over to PK tailored dosing for months 7-18. A comprehensive joint assessment involving bleed history, clinical examination, physical activity, specialist physiotherapy review, X-rays and MRI scanning of bilateral ankles, knees and elbow will be performed at months 0,6 and 18. Haemophilia Joint Health Score (HJHS), International Physical Activity (IPAQ) and EuroQoL 5-Dimensions (EQ5D) Questionnaires will also be performed at these three timepoints.

Clinical bleeds and FVIII usage will be recorded throughout the trial using the investigators Home Scan system, a smart phone application that allows patients to log factor VIII usage.

Results will be compared between both arms and between participants on primary and secondary prophylaxis. Information on those with naïve joints versus established arthropathy will be compared.

Due to the relative rarity of severe Haemophilia A the investigators plan to recruit 20 patients in total. All patients will act as their own control, crossing over from standard to PK tailored prophylaxis with joint assessments prior to crossover to allow comparison of the two regimes.

Conditions

Severe Haemophilia A

Keywords

Factor VIII deficiency; Arthropathy; MRI; XRay; Joint; HJHS

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Standard prophylaxis

Advate \[Antihemophilic Factor(Recombinant)\] 20-40 IU/kg 5-7 infusions per 14days

Group Type: ACTIVE_COMPARATOR

ADVATE [Antihemophilic Factor (Recombinant)]

Intervention Type: DRUG

In Arm 1 prior patients will be dosed as per body weight 20-40 IU/kg 5-7 infusions per fortnight

Pharmacokinetic tailored prophylaxis

Advate \[Antihemophilic Factor(Recombinant)\] dose determined by individual patient pharmacokinetics and infusions administerd on alternate days

Group Type: EXPERIMENTAL

ADVATE [Antihemophilic Factor (Recombinant)]

Intervention Type: DRUG

In Arm 2 patients who have completed arm 1 will cross over onto an individualised PK tailored alternate day dosing regimen

Interventions

ADVATE [Antihemophilic Factor (Recombinant)]

In Arm 1 prior patients will be dosed as per body weight 20-40 IU/kg 5-7 infusions per fortnight

Intervention Type: DRUG

ADVATE [Antihemophilic Factor (Recombinant)]

In Arm 2 patients who have completed arm 1 will cross over onto an individualised PK tailored alternate day dosing regimen

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male patients with severe Haemophilia A (baseline Factor VIII level of <0.01 IU/mL)
• Age 18 years and above
• Patients taking any regular prophylactic regimen (defined as regular factor VIII infusions, at least 5 times a fortnight, with the aim of minimising haemarthroses and other clinically significant bleeds).
• Low titre inhibitors, past history of an inhibitor, abnormal liver function, drugs that interfere with haemostasis and low Cluster of Differentiation 4 (CD4) counts are allowed.

Exclusion Criteria

• Presence of a target joint on prophylaxis (defined as 3 bleeds into one joint, during a 6 month period, during the last year).
• The occurrence of more than 3 haemarthroses in the last year that required more than 2 infusions to resolve.
• Patients with a learning disability or dementia
• Prisoners
• Adults who are unconscious/unable to give informed consent
• Participants with a pacemaker or implanted medical devices which are unsuitable to have a MRI will be excluded from the MRI scans during the trial but may proceed with other components.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Baxter BioScience

INDUSTRY

Sponsor Role: collaborator

St. James's Hospital, Ireland

OTHER

Sponsor Role: lead

Responsible Party

Dr. Niamh O'Connell

Consultant Haematologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Niamh M O'Connell, PhD, FRCPath

Role: PRINCIPAL_INVESTIGATOR

St. James's Hospital, Ireland

James O'Donnell, PhD, FRCPath

Role: PRINCIPAL_INVESTIGATOR

St. James's Hospital, Ireland

Locations

St. James's Hospital

Dublin, Dublin, Ireland

Site Status: RECRUITING

Countries

Ireland

Central Contacts

Michelle M Lavin, FRCPath

Role: CONTACT

Phone: +35314162142

Email: mlavin@stjames.ie

Niamh M O'Connell, FRCPath

Role: CONTACT

Phone: +35314162142

Other Identifiers

2013-003240-23

Identifier Type: -

Identifier Source: org_study_id