Clinical trial NCT02078427: ADVATE/ ADYNOVI Hemophilia A Outcome Database (AHEAD)
Official title: ADVATE/ ADYNOVI Hemophilia A Outcome Database
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2014-03-05
Enrollment: 951
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include male and female participants of any race and age who have a diagnosis of hemophilia A (Factor VIII (FVIII) =5%). Participants must have been prescribed rAHF-PFM or rAHF-PEG for the management of hemophilia A by the treating physician prior to the decision to enroll in the study.

Brief summary: The purpose of the study is to document the natural history of hemophilia A disease and long-term outcomes in terms of effectiveness, safety and quality of life in participants receiving Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) or Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG) in routine clinical practice


Eligibility criteria: Inclusion Criteria:

* Participant has hemophilia A {FVIII lesser than or equal to (\<=)5%}
* Participant is prescribed Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) or Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG) by the treating physician
* Participant or participant's legally authorized representative provides informed consent

Exclusion Criteria:

* Participant has known hypersensitivity to the active substance or any of the excipients
* Participant has known allergic reaction to mouse or hamster proteins
* Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving another FVIII concentrate or device during the course of this study

Primary outcomes:
measure: Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale
timeFrame: Up to approximately 12 years
Secondary outcomes:
measure: Annualized Bleed Rate, All Joints
timeFrame: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Annualized Bleed Rate, All Bleeds
timeFrame: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Annualized bleed rate, pre-existing target joints at baseline
timeFrame: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Incidence of New Target Joints
timeFrame: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Status of joint health by X-ray by Pettersson scale
timeFrame: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit.
measure: Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS)
timeFrame: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Status of joint health using the Hemophilia Joint Health Score (HJHS)
timeFrame: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Overall effectiveness assessment for prophylaxis therapy
timeFrame: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Compliance with the dosing prescribed and its relationship with effectiveness
timeFrame: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Overall effectiveness assessment for on-demand treatment
timeFrame: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Global effectiveness assessment for on-demand treatment
timeFrame: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Number of rAHF-PFM or rAHF-PEG units required for bleed cessation
timeFrame: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation
timeFrame: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy
timeFrame: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
measure: Incidence of pseudo tumor development
timeFrame: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Quality of Life: HAL questionnaire - for adult patients
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Quality of Life: SF-12v2 questionnaire - for adult patients
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Quality of Life: EQ-5D questionnaire - for adult patients
timeFrame: Enrollment visit;Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Quality of Life: PedHAL questionnaire - for pediatric patients
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Quality of Life: SF-10 questionnaire - for pediatric patients
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS)
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS)
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Number of days lost from school or work due to bleeding episodes
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 1
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 2
timeFrame: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels Lesser than (<)1%, Lesser Than or Equal to (<=) 2%, and <= 5% without history of inhibitor
timeFrame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% with history of inhibitor
timeFrame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
measure: Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5%
timeFrame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
measure: Incidence of therapy-related serious adverse events
timeFrame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
measure: Incidence of therapy-related non-serious adverse events
timeFrame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
measure: Incidence of inhibitors after switching to rAHF-PEG
timeFrame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Murdoch
country: Australia
facility: South Metropolitan Health Service trading as Fiona Stanley Hospital
state: Western Australia
city: Linz
country: Austria
facility: Landes Frauen und Kinderklinik Linz (LFKK Linz)
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Klinik für Kinder-und Jugendheilkunde
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Fortaleza
country: Brazil
facility: Hemoce - Ce
state: Ceará
city: Vitória
country: Brazil
facility: Hemocentro do Espírito Santo
state: Espírito Santo
city: Curitiba
country: Brazil
facility: Hemepar - Pr
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hemorgs - Rs
state: Parthenon
city: Belém
country: Brazil
facility: Fundação HEMOPA
state: Pará
city: Campinas
country: Brazil
facility: Hemocentro da UNICAMP
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hemocentro Ribeirão Preto - SP
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Hemorio - Rj
city: São Paulo
country: Brazil
facility: Faculdade de Medicina da Universidade de São Paulo
city: Edmonton
country: Canada
facility: Stollery Children's Hospital, University of Alberta
state: Alberta
city: Moncton
country: Canada
facility: The Moncton City Hospital
state: New Brunswick
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: St-Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sick Kids Hospital
state: Ontario
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
state: Futian
city: Guangzhou
country: China
facility: Nanfang Hospital Affiliated to Nanfang Medical University
state: Guangdong
city: Tianjin
country: China
facility: Institute of Hematology, Blood Disease Hospital, PUMC&CAMS
state: Heping
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Jinan
country: China
facility: The Blood Center of Shandong Province
state: Shandong
city: Beijing
country: China
facility: Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
city: Atlantico
country: Colombia
facility: IPS FUSA SAS Centro Integral de Coagulacion
city: Bogotá
country: Colombia
facility: Integral Solutions SD SAS
city: Floridablanca
country: Colombia
facility: Fundación Oftalmológica de Santander FOSCAL
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno
city: Ostrava
country: Czechia
facility: Fakultní nemocnice Ostrava, Oddělení dětské hematologie a hematoonkologie
city: Ostrava
country: Czechia
facility: Fakultní nemocnice Ostrava
city: Praha 5
country: Czechia
facility: Fakultní nemocnice v Motole
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Brest
country: France
facility: "Hôpital Morvan CHRU de Brest"
city: CAEN Cedex
country: France
facility: CHU Côte de Nacre - CRTH
city: Chambery Cedex
country: France
facility: Centre Hospitalier Générale - CTH
city: Dijon Cedex
country: France
facility: CTRH - CHU Bocage
city: Le Chesnay Cedex
country: France
facility: Hôpital André Mignot
city: LIMOGES cedex
country: France
facility: Hôpital de la Mère et de l'Enfant - CHU de LIMOGES
city: Nantes Cedex
country: France
facility: CHRU Hôtel Dieu - CRTH
city: Paris
country: France
facility: Hôpital Cochin
city: Reims Cedex
country: France
facility: CHU de Reims Hôpital Maison Blanche - CRTH
city: RENNES Cedex 09
country: France
facility: Centre Régional de Traitement de l'Hémophilie et des Maladies hémorragiques. CHU de Rennes - Hôpital Pontchaillou
city: Rouen
country: France
facility: CHRU Charles Nicolle
city: Saint Priest en Jarez
country: France
facility: CIC
city: Toulouse Cedex 9
country: France
facility: CHRU Purpan CRTH - Pavillon Sénac
city: Goudi
country: Greece
facility: Aghia Sofia Children's Hospital
state: Athens
city: Goudi
country: Greece
facility: Laikon General Hospital
state: Athens
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "Ippokratio"
city: Budapest
country: Hungary
facility: Heim Pál Gyermekkórház
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Mohács
country: Hungary
facility: Mohács City Hospital
city: Nyíregyháza
country: Hungary
facility: Jósa András County Hospital
city: Szombathely
country: Hungary
facility: Markusovszky Hospital
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Consorziale Di Bari
city: Bologna
country: Italy
facility: Policlinico S Orsola Malpighi
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Vittorio Emanuele, Ferrarotto, S. Bambino
city: Catanzaro
country: Italy
facility: Ospedale Pugliese -Ciaccio
city: Firenze
country: Italy
facility: Az. Osp. Univ. Careggi
city: Macerata
country: Italy
facility: Ospedale di Macerata
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova Clinica Medica II
city: Palermo
country: Italy
facility: AOUP P. Giaccone
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi Melacrino Morelli
city: Roma
country: Italy
facility: Università degli studi di Roma "La Sapienza"
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli
city: Scorrano
country: Italy
facility: Centro Emofilia e Coagulopatie Rare
city: Torino
country: Italy
facility: Ospedale Molinette
city: Oslo
country: Norway
facility: Rikshospitalet
city: Oslo
country: Norway
facility: Rikshospitalet, Oslo University Hospital
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. dr Andrzeja Jurasza
city: Gdansk
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny we Wrocławiu
city: Ponta Delgada
country: Portugal
facility: Hospital do Divino Espírito Santo
state: Açores
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitade de Coimbra
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte Hospital de Sta. Maria
city: Porto
country: Portugal
facility: Centro Hospitalar de São João, E.P.E.
city: Chelyabinsk
country: Russian Federation
facility: SBHI Chelyabinsk Regional Children's Clinical Hospital
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "Hematology Research Center" of Ministry of Healthcare of Russian Federation
city: Petrozavodsk
country: Russian Federation
facility: SBHI of the Republic of Kareliya Republican Hospital n.a. V.A. Baranov
city: Saint Petersburg
country: Russian Federation
facility: State Budget Healthcare Institution of Saint-Petersburg "City polyclinic #37"
city: Samara
country: Russian Federation
facility: Clinics of FSBEI High Education Samara SMU of MoH of Russia
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera-Materno Infantil
city: Barcelona
country: Spain
facility: Hospital Hospital Sant Joan de Déu
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron (HUVH)
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Malmö
country: Sweden
facility: Kliniska studier i Sverige - Forum Söder
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Luzern 17
country: Switzerland
facility: Luzerner Kantonsspital
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Wabern
country: Switzerland
facility: FMH Kinder und Jugendmedizin, im Wabern-Zentrum
city: Zürich
country: Switzerland
facility: Kinderspital Zürich
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital
state: Hampshire
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital NHS Foundation Trust, Addenbrooke's Hospital
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University Foundation Trust, Kent & Canterbury Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: