The Hemophilia Ultrasound Project



Status:Recruiting
Conditions:Anemia, Hematology
Therapuetic Areas:Hematology
Healthy:No
Age Range:Any
Updated:9/14/2018
Start Date:July 2016
End Date:July 2021
Contact:Fernando F Corrales-Medina, MD
Email:ffc5@med.miami.edu
Phone:305-243-8652

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Evaluation of Joint Arthropathy Using Ultrasound Technique in Children With Severe Hemophilia Undergoing Prophylaxis Regimen

To evaluate the prevalence of subclinical arthropathy in children with severe hemophilia
undergoing a prophylaxis regimen and without evidence of target joints, using a validated
ultrasound scoring method.

Persons with Hemophilia (A or B) often experience recurrent joint bleeds, most commonly
affecting the ankles, knees and elbows. These bleeds can lead to significant pain and
disability over time. If recurrent joint bleeds are not managed with prompt and adequate
infusions of factor concentrate, the damage caused by the presence of blood in the joint
space will eventually result in a condition called debilitating chronic hemophilic
arthropathy.

The initiation of and adherence to a prophylactic infusion regimen, starting with the first
or second joint bleed, is essential for prevention of progression to arthropathy.

Studies have demonstrated that prophylaxis with recombinant or plasma-derived factor VIII or
IX concentrates is effective in preventing clinical joint bleeds and the progression to
debilitating joint disease in patients with severe hemophilia A or B respectively. However,
for patients on prophylaxis, the absence of symptomatic joint bleeds and/or structural and
functional abnormalities of joints on physical examination and plain radiographic images can
lead to the erroneous assumption that the prophylaxis is completely effective. It has been
established that patients with severe hemophilia are still at risk for subclinical bleeding
("microbleeds") despite seemingly adequate prophylaxis.

Young adults, despite a lifetime on prophylaxis and apparently normal joints are developing
arthropathy in their 20's and 30's. Prophylaxis as currently practiced may only be delaying
the onset of clinical joint disease.

The recent advancements in ultrasound imaging (US) have been proven to be effective in
confirming a joint bleed, monitoring the evolution of a joint bleed and assessing the
resolution or recurrence of a bleed. Previous studies have evaluated the prevalence of
subclinical arthropathy in young hemophilic adults using both US and MRI techniques and
concluded that US is as effective and sensitive as MRI identifying these subclinical joint
abnormalities.

However, to the investigators' knowledge, no prior studies have used US technique over an
extended period of time to monitor the natural evolution of joint arthropathy in children
with hemophilia who are adherent to an established prophylaxis regimen and have no evidence
of clinical joint compromise.

The seminal Joint Outcome Study, which confirmed the role of prophylaxis in preventing overt
clinical joint disease, mandated a trough residual factor VIII level of 1%. While this trough
level significantly decreased overt hemarthroses and joint damage, the evidence suggestive of
microbleeds raised a question as to the protection afforded by such a low trough level.
Intuitively it would seem as if a higher trough level should confer greater protection
against microbleeds, and result in more sustainable joint health. The "ideal" protective
trough, has not been established.

The investigators' hypothesis is that US is a valuable imaging technique to monitor the
natural evolution of hemophilic arthropathy in children with severe hemophilia A or B who are
undergoing prophylaxis regimen and do not manifest clinical evidence of hemophilic
arthropathy.

Through this observational study, the investigators will provide valuable information in
regards the prevalence, progression and severity of joint abnormalities. The use of US to
detect microbleeds before the cumulative damaging effects demonstrable by MRI, will also
allow tailoring of treatment and the implementation of new prophylaxis strategies.

Inclusion Criteria:

- Severe Hemophilia Cohort:Patients from 0 up to 30 months of age with diagnosis of
severe hemophilia A or B defined as a factor VIII:C/IX:C of <1% undergoing prophylaxis
regimen with any factor VIII or IX concentrate and without evidence (clinical or by
history) of target joint disease.

- Mild/moderate Hemophilia Cohort:Patients from 0 up to 30 months of age with diagnosis
of mild hemophilia A or B defined as a factor VIII:C/IX:C of 5-50% and those with
diagnosis of moderate hemophilia A or B defined a s a factor VIII:C/IX:C of 1-5%
without evidence (clinical or by history) of target joint disease and no history of
spontaneous joint bleeds.

Exclusion Criteria:

- Patients with concomitant Hepatitis B, Hepatitis C and HIV viral infections (because
of a recognized arthritogen effect).

- Present or prior history of anti FVIII or IX inhibitors.

- Known inflammatory joint disease.

- Established target joint.
We found this trial at
4
sites
Gainesville, Florida 32610
(352) 392-3261
Principal Investigator: Tung T Wynn, MD
Phone: 352-273-9050
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
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Lexington, Kentucky
859) 257-9000
Principal Investigator: Vlad C Rudelescu, MD
University of Kentucky The University of Kentucky is a public, land grant university dedicated to...
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Lexington, KY
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Miami, Florida 33136
Phone: 305-243-6925
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New Orleans, Louisiana 70112
Principal Investigator: Tammuella C Singleton, MD
Phone: 504-988-3596
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New Orleans, LA
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