Clinical trial NCT04055051: ATHN 11: Liver Transplantation Outcomes Study
Official title: An Observational Cohort Study of Long-Term Outcomes of Orthotopic Liver Transplantation in People With Hemophilia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia A and B
Liver Transplantation
Keywords: Hemophilia A
Hemophilia B
Liver Transplantation
Quality of Life
Hemophilia Treatment Centers (HTCs)
Lead sponsor: American Thrombosis and Hemostasis Network
Sponsor class: NETWORK
Collaborators: name: BioMarin Pharmaceutical
First posted: 2019-08-13
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will enroll a cohort of approximately 112 participants born with hemophilia who meet the eligibility criteria and are receiving care from one of approximately 12 participating HTCs. The participants will be approached for enrollment and matched 1:3 with age-, race-, ethnicity-matched controls (N=84) with hemophilia who have not undergone transplantation, for a total of 112 individuals with hemophilia who will compete quality of life questionnaires.

Brief summary: This study is designed as a multi-center, observational cohort study of participants with hemophilia A and B who have and have not undergone liver transplantation. Participants will be asked to complete health related quality of life questionnaires and provide medical history.

Detailed description: At a time when gene therapy is becoming a reality for individuals with hemophilia A and B, little is known about long-term cures. Yet, there are few data to provide real life testing of the impact of long-term cures. Specifically, little is known about the relationship between factor level achieved with gene therapy and clinical outcomes or quality of life. The analogy to liver transplant is clear. There has been no systematic method to collect and analyze the long-term outcomes of liver transplantation in individuals with hemophilia. Previous efforts to access data through the United Network for Organ Sharing national database have been complicated by lack of identification of those with hemophilia. As most of the individuals with hemophilia who undergo liver transplantation receive care at a hemophilia treatment center (HTC), ATHN proposes to leverage its existing relationship with the HTCs to support HTC execution of this study.

ATHN, in collaboration with US Hemophilia Treatment Centers (HTCs), can provide the infrastructure and organization to support a longitudinal cohort study of subjects with congenital hemophilia who have and have not undergone liver transplantation. This cohort study will compare quality of life outcomes between cases that have undergone liver transplantation and controls that have not undergone liver transplantation. The study will determine if factor levels attained post-transplantation correlate with or predict improvement in quality of life measures.

The existence of ATHN and the ATHN System for clinical care and research provides an opportunity to observe a cohort of subjects after liver transplantation with facility. During the study period, it is predicted that sustained normalization in factor VIII or IX levels following liver transplantation improves clinical functioning and quality of life in adults with hemophilia A and B.

All study related contact will be timed to coincide with routine, scheduled care whenever possible. The study schedule will include:

Study enrollment - Study activities will begin after participant consent. Activities include the documentation of relevant medical history and the administration of quality of life (QoL) questionnaires.

Participants will be asked to complete health related (QoL) questionnaires and provide medical history. These questionnaires include:

1. Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL): A quality of life questionnaire designed to asses health-related quality of life in adult patients with hemophilia. Domains include physical health, feelings, view of self, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, and partnership and sexuality.
2. Patient Reported Outcomes Measurement Information System (PROMIS-29): A quality of life questionnaire designed to assess physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference, and pain intensity.
3. Hemophilia Orthotopic Liver Transplantation QoL Questionnaire (HOT): A quality of life questionnaire, adapted from a cancer survivorship tool, designed to assess adults with hemophilia who have received a liver transplant. Domains include physical well-being, psychological well-being, stress, anxiety, fear, work, family, relationships, and spiritual well-being.

Eligibility criteria: Inclusion Criteria

Participants who meet the following inclusion criteria are eligible for enrollment into the study:

1. Congenital hemophilia A or B of any severity, who have and have not undergone a liver transplant;
2. Age \> 18; and
3. Sex assigned at birth was male

Exclusion Criteria

Participants who fall into any of the following exclusion criteria at the time of screening are not eligible for enrollment into the study:

1. Age \<18.

Primary outcomes:
measure: Quality of life (Haem-A-QoL)
timeFrame: 1 year
measure: Quality of life (PROMIS-29)
timeFrame: 1 year
measure: Quality of Life (HOT)
timeFrame: 1 year
Secondary outcomes:
measure: Clotting factor protein
timeFrame: 1year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Institute for Children Hemophilia Program
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center (IHTC)
state: Indiana
city: Scarborough
country: United States
facility: Maine Hemophilia and Thrombosis Center
state: Maine
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Comprehensive Hemophilia Center
state: Minnesota
city: Rochester
country: United States
facility: Mary M. Gooley Hemophilia Center, Inc.
state: New York
city: Chapel Hill
country: United States
facility: Comprehensive Hemophilia Treatment Center, University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center Hemophilia Treatment Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Gulf States Hemophilia and Thrombophilia Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Center for Bleeding and Clotting Disorders
state: Utah
city: Green Bay
country: United States
facility: Hemophilia Outreach Center Green Bay
state: Wisconsin
city: Milwaukee
country: United States
facility: Comprehensive Center for Bleeding Disorders, Milwaukee
state: Wisconsin
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Margaret Ragni, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Madeira CL, Layman ME, de Vera RE, Fontes PA, Ragni MV. Extrahepatic factor VIII production in transplant recipient of hemophilia donor liver. Blood. 2009 May 21;113(21):5364-5. doi: 10.1182/blood-2009-02-206979. No abstract available.
citation: Subramanian A, Sulkowski M, Barin B, Stablein D, Curry M, Nissen N, Dove L, Roland M, Florman S, Blumberg E, Stosor V, Jayaweera DT, Huprikar S, Fung J, Pruett T, Stock P, Ragni M. MELD score is an important predictor of pretransplantation mortality in HIV-infected liver transplant candidates. Gastroenterology. 2010 Jan;138(1):159-64. doi: 10.1053/j.gastro.2009.09.053. Epub 2009 Sep 30.
citation: Ragni MV, Moore CG, Soadwa K, Nalesnik MA, Zajko AB, Cortese-Hassett A, Whiteside TL, Hart S, Zeevi A, Li J, Shaikh OS; HHH Study Group. Impact of HIV on liver fibrosis in men with hepatitis C infection and haemophilia. Haemophilia. 2011 Jan;17(1):103-11. doi: 10.1111/j.1365-2516.2010.02366.x. Epub 2010 Aug 16.
citation: Ragni MV, Devera ME, Roland ME, Wong M, Stosor V, Sherman KE, Hardy D, Blumberg E, Fung J, Barin B, Stablein D, Stock PG. Liver transplant outcomes in HIV+ haemophilic men. Haemophilia. 2013 Jan;19(1):134-40. doi: 10.1111/j.1365-2516.2012.02905.x. Epub 2012 Jul 5.
citation: Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, Ragni MV, Barin B, Simon D, Olthoff KM, Johnson L, Stosor V, Jayaweera D, Fung J, Sherman KE, Subramanian A, Millis JM, Slakey D, Berg CL, Carlson L, Ferrell L, Stablein DM, Odim J, Fox L, Stock PG; Solid Organ Transplantation in HIV: Multi-Site Study Investigators. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transpl. 2012 Jun;18(6):716-26. doi: 10.1002/lt.23411.
citation: Aguero F, Rimola A, Stock P, Grossi P, Rockstroh JK, Agarwal K, Garzoni C, Barcan LA, Maltez F, Manzardo C, Mari M, Ragni MV, Anadol E, Di Benedetto F, Nishida S, Gastaca M, Miro JM; FIPSE/NIH HIVTR/NEAT023 Investigators. Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study. Am J Transplant. 2016 Feb;16(2):679-87. doi: 10.1111/ajt.13461. Epub 2015 Sep 28.
citation: Mehta KD, Ragni MV. Bleeding and liver transplantation outcomes in haemophilia. Haemophilia. 2017 Mar;23(2):230-237. doi: 10.1111/hae.13104. Epub 2016 Nov 4.
citation: Ragni MV, Humar A, Stock PG, Blumberg EA, Eghtesad B, Fung JJ, Stosor V, Nissen N, Wong MT, Sherman KE, Stablein DM, Barin B. Hemophilia Liver Transplantation Observational Study. Liver Transpl. 2017 Jun;23(6):762-768. doi: 10.1002/lt.24688.
citation: Ragni MV, Nalesnik MA, Schillo R, Dang Q. Highly active antiretroviral therapy improves ESLD-free survival in HIV-HCV co-infection. Haemophilia. 2009 Mar;15(2):552-8. doi: 10.1111/j.1365-2516.2008.01935.x.