Research Studies

Dr. Jonathan Roberts is currently a pediatric hematology and oncology fellow with the Medical College of Wisconsin and the Children's Hospital of Wisconsin. His fellowship mentor will be Joan Gill, MD, Professor of Pediatrics at the Medical College of Wisconsin and Director of the Comprehensive Center for Bleeding Disorders (CCBD) at the BloodCenter of Wisconsin. Roberts graduated with honors from Greenville College, Illinois, and received his MD from Southern Illinois University School of Medicine. He did his residency in Pediatrics at the University of Illinois at Peoria and Children's Hospital of Illinois, where he also distinguished himself, receiving awards of excellence for critical care and research. During his pediatric residency, Roberts worked with Dr. Michael Tarantino to initiate a clinical research trial to assess the role of FXIII on intraventricular hemorrhage in premature, low birth weight infants. As a NHF-Baxter Clinical Fellow, Roberts will receive focused training and gain clinical experience through the hemostasis clinics at CCBD and further develop his research skills in a project to develop a new ELISA-based assay for assigning VWF phenotype. Roberts has plans to pursue a Master's Degree in Clinical and Translational Science. His goal is to become an expert physician/scientist with a long-term career focus on hemophilia, and other bleeding and clotting disorders.

As technology advances and provides electronic tools for enhancing communication by phone and computer, health care providers are finding ways to adapt these tools into patient care. Telehealth is the use of electronic information and telecommunications technologies to support long-distance clinical health care. For patients with hemophilia who experience a bleed in the home setting, telehealth has the potential to help the patient, family, and health care provider assess what is going on and develop the best plan of care, all while the patient stays in the home setting. In this clinical project, we will use the telehealth resources available at our institution to partner with patients and families with severe hemophilia with a high risk of bleeding episode who also have a home computer with a camera and internet access. We want to find out more about how many patients have these home resources, how to use video-conferencing when managing a bleed and what patients, families, and health care staff think about using video conferencing. This will help us plan future research using telehealth video-conferencing for a larger group of hemophilia patients.

Dr. Tammuella Chrisentery-Singleton is an Assistant Professor of Clinical Pediatrics at Tulane University and is board certified in pediatric hematology/oncology. She will receive training under the mentorship of Cindy Leissinger, MD, Chief, Section of Hematology & Medical Oncology at Tulane University School of Medicine and Director of the Louisiana Center for Bleeding and Clotting Disorders. Chrisentery-Singleton graduated with honors from Xavier University, received her MD from Louisiana State University and then completed her pediatric residency at the University of Miami. Following residency, she completed pediatric hematology/oncology fellowship training at Johns Hopkins University, where she worked with Dr. Jim Cassella and developed a serious interest in disorders of coagulation, particularly hemophilia. After her fellowship training, she was recruited to join the pediatric hematology/oncology faculty at LSU and Children's Hospital of New Orleans. In 2010, Chrisentery-Singleton accepted a position at Tulane University because of her desire to receive more training and spend more time in the specialized coagulation medicine program. As an NHF-Baxter Clinical Fellow, she will receive dedicated training in bleeding and clotting disorders for both children and adult patients, along with mentoring in clinical research related to bleeding disorders. She will also continue her work on several ongoing clinical trials, and pursue her project in developing models to better determine pharmacokinetic parameters with a minimal number of needle sticks in pediatric patients with hemophilia. Her goals are to steadily improve her knowledge and skills in caring for patients with coagulation disorders, and continue building her academic career in coagulation medicine.

Objective:

When a surgical procedure is required in a patient with hemophilia, continuous infusion of factor (CIF) is a safe and effective alternative to bolus dosing.1-5 However, when cultural values collide with best practices, a patient-centered collaborative care plan is necessary to help ensure a positive outcome while respecting the core values of the patient.

Method:

Our team collaborated with our local Hemophilia Treatment Center (HTC) physicians and nurses to plan CIF for an Amish patient who required a total knee replacement. After interviewing the patient, the care team recognized when the patient transitioned on CIF to the home, we would need to respect the cultural beliefs of the patient without compromising the care.

The HTC physician and nurse ordered continuous infusion of factor for the patient with goal factor levels to remain between 70-100% on post-op days 1-7 and between 50-70% on post- op days 8-14. The home infusion team collaborated with the family and HTC team to finalize the care plan. The patient-centered decision prompted the use of a battery powered ambulatory infusion pump and the use of pre-approved sliding scale factor orders (ACAT protocol) with daily factor levels. Our biggest barrier was in respect to communication with the patient. In our local Amish community, telephones are not accessible. Our brainstorming lead to our COO suggesting we include a battery operated phone that would be attached to the pump and only be used for pump emergencies.

Summary:

The patient was discharged to home post-op day three with recombinant factor VIII running at 2.5 units/kg/hour via a battery operated ambulatory pump. Levels on post-op day four were below 70, prompting the nurse to call on the “pump phone” and return for a visit that night to increase the rate to 2.7 units/kg/hour. The rate remained the same throughout the remainder of the therapy and the levels stayed within the range designated by the physician.

Conclusion:

The patient-centered multidisciplinary care plan allowed for a positive outcome while respecting the patient’s culture.

Objective:

This prospective clinical trial was conducted to assess the safety, efficacy and PK of BAX326 (a novel recombinant FIX [rFIX] manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps [solvent/detergent treatment and nanofiltration]) in previously-treated patients aged 12 to 65 with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B.

Methods:

Hemostatic efficacy after twice weekly prophylaxis with BAX326 was determined in terms of annualized bleeding rate (ABR) compared with a historical control group treated on- demand. PK equivalence was assessed between BAX326 and a commercial rFIX in a crossover design. Safety was evaluated by the occurrence of adverse events.

Summary:

In subjects on twice weekly prophylaxis with BAX326 over at least 3 months (N=56), 24 (43%) did not bleed throughout the study observation period, and the ABR was substantially lower when compared with a historical control group (79% reduction, p<0.001). Joint bleeds (major joints: wrist, elbow, shoulder, hip, knee, ankle) occurred at a mean ABR of 2.85 ± 4.25 compared with 1.41 ± 2.87 in non-joint bleed sites. Of the 32/56 subjects with bleeds, 90.6% (29/32) had arthropathy at screening and only 28.1% (9/32) did not have target joints, as compared to subjects without bleeds, of whom 79.2% (19/24) had arthropathy and 50% (12/24) did not have target joints at screening. Higher mean ABRs were observed in subjects with arthropathy (N=46) versus without arthropathy (N=8) (4.54 vs. 2.57 for all bleeds, 3.16 vs. 1.02 for joint bleeds, and 1.97 vs. 0.25 for spontaneous bleeds). A similar pattern was observed for the ABRs of joint bleeds and spontaneous bleeds in subjects with target joints (N=35) (mean ABR: 2.41 ± 3.79) and those with no target joints (N=21) (mean ABR: 0.58 ± 1.63). Most bleeds were controlled with 1-2 infusions of BAX326 and with an efficacy rating of “excellent.” BAX326 was equivalent to the comparator rFIX in terms of AUC 0 72 h /dose. BAX326 is safe and well tolerated in hemophilia B patients, with no signs of immunogenicity or thrombotic events.

Conclusions:

BAX326 has a positive safety profile and is efficacious in treating bleeds and in routine prophylaxis in PTPs aged ≥12 years with hemophilia B. The results also demonstrate that subjects with target joints and hemophilic arthropathy receiving secondary prophylaxis tend to have higher ABRs as compared to those without these underlying conditions.

In the long-term, Dr. Ivanciu's goals include the establishment of an independent research laboratory to focus on better understanding the pathological consequences of disruptions in the hemostatic balance. She believes that, as a past JGP Fellow, she is in a unique position to make meaningful contributions to the field of hematology and possibly help advance new therapies for the treatment of hemophilia.