ADVATE/ ADYNOVI Hemophilia A Outcome Database (AHEAD)
- Conditions
- Hemophilia A
- Interventions
- Biological: ADVATEBiological: ADYNOVI
- Registration Number
- NCT02078427
- Lead Sponsor
- Baxalta now part of Shire
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 951
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description rAHF-PFM ADVATE Participants treated with rAHF-PFM alone rAHF-PFM then rAHF-PEG ADYNOVI Participants treated with rAHF-PFM and subsequently switched to rAHF-PEG rAHF-PEG ADYNOVI Participants treated with rAHF-PEG alone rAHF-PFM then rAHF-PEG ADVATE Participants treated with rAHF-PFM and subsequently switched to rAHF-PEG
- Primary Outcome Measures
Name Time Method Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale Up to approximately 12 years The World Federation of Hemophilia developed a musculoskeletal evaluation system, commonly referred to as the Gilbert test, to measure hemophilia joint health status.The Gilbert test needs to be performed in the absence of acute bleed, acute pain, and acute inflammation into the evaluated joint. Four parameters are used in each Gilbert test: pain (score: 0-3), bleeding (score: 0-3), physical exam (score: 0-12), and X-ray evaluation (score: 0-13) Scores of 0, represent no pain, no bleeding, no physical exam issues, and/or no x-ray issues. Higher scores for each of these categories represents worsening conditions.
- Secondary Outcome Measures
Name Time Method Annualized Bleed Rate, All Bleeds 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 The annualized bleed rate for all bleeds will be calculated per participant and summarized over the set of available participants.with a minimum observation period of 90 days per treatment regimen.
Annualized bleed rate, pre-existing target joints at baseline 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 The annualized bleed rate for pre-existing target joints at baseline will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.
Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation 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 Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) Number of days lost from school or work due to bleeding episodes 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 Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients 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 The EQ-5D measures health utility in subjects aged 14 and up.
Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% with history of inhibitor Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) Incidence of inhibitors after switching to rAHF-PEG Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) Incidence of inhibitors after switching to rAHF-PEG in the same subgroups of patients
Modalities of switching from a standard FVIII product to rAHF-PEG - 1 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 Difference in number of weekly prophylactic infusions between previous regimen and rAHF-PEG
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 Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) Incidence of therapy-related serious adverse events Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) Incidence of therapy-related non-serious adverse events Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) Annualized Bleed Rate, All Joints 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 The annualized bleed rate for all joints will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.
Status of joint health by X-ray by Pettersson scale 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. The status of joint health by X-ray by Pettersson score will be summarized for each observational year.
Overall effectiveness assessment for on-demand treatment 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 * Excellent: Bleed episodes typically respond to same or fewer number of infusion and same or lower dose as compared with previous on-demand treatment or investigator's expectation
* Good: Most bleed episodes typically respond to same number of infusion and dose but some require more infusions or higher dose as compared with previous on-demand treatment or investigator's expectation
* Fair: Bleed episodes typically require more infusions and/or higher dose than expected as compared with previous on-demand treatment or investigator's expectation
* Poor: Bleed episodes routinely fail to respond to same number of infusion and dose and require additional or different factor concentrate for hemostatic control as compared with previous on-demand treatment or investigator's expectationIncidence of New Target Joints 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 The incidence of new target joints will be calculated as the total number of new target joints in all participants divided by the total number of observation days.
Compliance with the dosing prescribed and its relationship with effectiveness 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 Evaluation of patients´ compliance to prescribed prophylactic treatment will be performed by the treating physician. Compliance will be categorized according to a 4-point table (Highly compliant, Fairly compliant, Moderately compliant, Poorly compliant)
Overall effectiveness assessment for prophylaxis therapy 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 * Excellent: Same or lower breakthrough bleed rate (BBR) within last 12 months (M) compared with prior prophylaxis; if participant did not receive prior prophylaxis with rAHF-PFM, rAHF-PEG or other Factor VIII (FVIII), same or better than expected outcome according to investigator's expectation
* Good: Minor increase in BBR within last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, slightly less than expected outcome according to investigator's expectation
* Fair: Moderate increase in BBR in last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, somewhat less than expected outcome according to investigator's expectation
* Poor: Significant increase in BBR in the 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, little to no benefit according to investigator's expectationStatus of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS) 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 LSS score format= A(e:s:h). Sum of values for Subchondral Cyst (score: 1-6), irregularity/erosion of Subchondral Cortex (score: 1-4), and Chondral Destruction (score: 1-6) gives value for the A component of score. e, s, h components represent effusion/hemarthrosis, hypertrophic synovial, \& hemosiderin deposition (score: 0-4 for each). Max. score is 16(4:4:4).
Subchondral Cyst:
* ≥1 bone
* ≥2 bones
* \>3 cysts in ≥1 bone
* \>3 cysts ≥2 bones
* Largest size \>4 mm: ≥1 bone
* Largest size \>4 mm: ≥2 bones
Subchondral Cortex
* ≥1 bone
* ≥2 bones
* Involve \> half joint surface: ≥1 bone
* Involve \> half of joint surface: ≥2 bones
Chondral Destruction
* ≥1 bone
* ≥2 bones
* Full thickness defect (FTD): ≥1 bone
* FTD: ≥2 bones
* FTD involves \>1/3 of joint surface: ≥1 bone
* FTD involves \>1/3 of joint surface: ≥2 bones
Effusion/hemarthrosis (e): Hypertrophic synovial (s): Hemosiderin (h): (0-4 for each):
* 0 absent
* 1 equivocal
* 2 small
* 3 moderate
* 4 largeStatus of joint health using the Hemophilia Joint Health Score (HJHS) 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 The International Prophylaxis Study Group (IPSG) developed a scoring system for musculoskeletal evaluation, the HJHS, optimized for use in children with no or minimal joint disease.
The HJHS includes the following parameters: swelling, duration of swelling, muscle atrophy, joint pain, crepitus on motion, flexion loss, extension loss, strength and global gait.Number of rAHF-PFM or rAHF-PEG units required for bleed cessation 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 Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy 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 Quality of Life: HAL questionnaire - for adult patients 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 The the lHAL measures activities involving the upper extremities, basic activities involving ower extremities and complex activities involving the lower extremities as well as an overall physical activity score for adults.
Global effectiveness assessment for on-demand treatment 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 * Excellent: Full relief of pain and cessation of bleeding as evidenced by objective signs (e.g., swelling, tenderness, irritability, inconsolability, and decreased range of motion in the case of musculoskeletal hemorrhage) within approximately 8 hours of a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring.
* Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after the infusion. Possibly requires more than 1 infusion for complete resolution.
* Fair: Probable or slight relief of pain and slight improvement in signs of bleeding within approximately 8 hours after the infusion. Requires more than 1 infusion for complete resolution.
* Poor: No improvement or condition worsens.Quality of Life: EQ-5D questionnaire - for adult patients 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 The EQ-5D measures health utility in adult participants.
Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS) 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 The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain).
Participants will be asked to provide ratings on level of acute pain associated with each bleeding episode using the VAS. The VAS scores will be recorded in the participant diary.Incidence of pseudo tumor development 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 Quality of Life: SF-12v2 questionnaire - for adult patients 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 The SF-12v2 measures generic health-related quality of life for adults.
Quality of Life: PedHAL questionnaire - for pediatric patients 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 The PedHAL measures activities involving the upper extremities, basic activities involving the lower extremities and complex activities involving the lower extremities as well as an overall physical activity score for children.
For participants 4-13 years of age:
- PedHAL (parent version)
For participants 14-17 years of age:
- PedHAL (child version)Quality of Life: SF-10 questionnaire - for pediatric patients 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 The SF-10 measures generic health-related quality of life for children and is parent-completed.
Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS) 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 The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain).
During screening visit and on an annual basis, the investigators shall ask participants to rate the average level of chronic pain associated with hemophilia over the period of 4 weeks prior to visit date using the VAS.Modalities of switching from a standard FVIII product to rAHF-PEG - 2 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 Difference in number of weekly doses between previous regimen and rAHFPEG
Trial Locations
- Locations (110)
Hôpital André Mignot
🇫🇷Le Chesnay Cedex, France
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Medizinische Universitaet Wien
🇦🇹Wien, Austria
Hemepar - Pr
🇧🇷Curitiba, Paraná, Brazil
Hemorio - Rj
🇧🇷Rio de Janeiro, Brazil
Hemocentro Ribeirão Preto - SP
🇧🇷Ribeirão Preto, São Paulo, Brazil
Faculdade de Medicina da Universidade de São Paulo
🇧🇷São Paulo, Brazil
Stollery Children's Hospital, University of Alberta
🇨🇦Edmonton, Alberta, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
St-Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Sick Kids Hospital
🇨🇦Toronto, Ontario, Canada
Royal University Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Shenzhen Children's Hospital
🇨🇳Shenzhen, Futian, China
Nanfang Hospital Affiliated to Nanfang Medical University
🇨🇳Guangzhou, Guangdong, China
Institute of Hematology, Blood Disease Hospital, PUMC&CAMS
🇨🇳Tianjin, Heping, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology
🇨🇳Wuhan, Hubei, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
The Blood Center of Shandong Province
🇨🇳Jinan, Shandong, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, China
Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
🇨🇳Beijing, China
IPS FUSA SAS Centro Integral de Coagulacion
🇨🇴Atlantico, Colombia
Integral Solutions SD SAS
🇨🇴Bogotá, Colombia
Fundación Oftalmológica de Santander FOSCAL
🇨🇴Floridablanca, Colombia
Fakultní nemocnice Brno
🇨🇿Brno, Czechia
Fakultní nemocnice Ostrava, Oddělení dětské hematologie a hematoonkologie
🇨🇿Ostrava, Czechia
Fakultní nemocnice v Motole
🇨🇿Praha 5, Czechia
Fakultní nemocnice Ostrava
🇨🇿Ostrava, Czechia
CHU Côte de Nacre - CRTH
🇫🇷CAEN Cedex, France
"Hôpital Morvan CHRU de Brest"
🇫🇷Brest, France
CTRH - CHU Bocage
🇫🇷Dijon Cedex, France
Centre Hospitalier Générale - CTH
🇫🇷Chambery Cedex, France
Hôpital de la Mère et de l'Enfant - CHU de LIMOGES
🇫🇷LIMOGES cedex, France
Hôpital Cochin
🇫🇷Paris, France
CHRU Hôtel Dieu - CRTH
🇫🇷Nantes Cedex, France
CHU de Reims Hôpital Maison Blanche - CRTH
🇫🇷Reims Cedex, France
Centre Régional de Traitement de l'Hémophilie et des Maladies hémorragiques. CHU de Rennes - Hôpital Pontchaillou
🇫🇷RENNES Cedex 09, France
CHRU Charles Nicolle
🇫🇷Rouen, France
Aghia Sofia Children's Hospital
🇬🇷Goudi, Athens, Greece
CIC
🇫🇷Saint Priest en Jarez, France
Mohács City Hospital
🇭🇺Mohács, Hungary
Jósa András County Hospital
🇭🇺Nyíregyháza, Hungary
Markusovszky Hospital
🇭🇺Szombathely, Hungary
Azienda Ospedaliera Universitaria Vittorio Emanuele, Ferrarotto, S. Bambino
🇮🇹Catania, Italy
Ospedale di Macerata
🇮🇹Macerata, Italy
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
Rikshospitalet
🇳🇴Oslo, Norway
Szpital Uniwersytecki nr 1 im. dr Andrzeja Jurasza
🇵🇱Bydgoszcz, Poland
Rikshospitalet, Oslo University Hospital
🇳🇴Oslo, Norway
Centro Hospitalar de São João, E.P.E.
🇵🇹Porto, Portugal
Federal State Budget Institution "Hematology Research Center" of Ministry of Healthcare of Russian Federation
🇷🇺Moscow, Russian Federation
SBHI of the Republic of Kareliya Republican Hospital n.a. V.A. Baranov
🇷🇺Petrozavodsk, Russian Federation
State Budget Healthcare Institution of Saint-Petersburg "City polyclinic #37"
🇷🇺Saint Petersburg, Russian Federation
Clinics of FSBEI High Education Samara SMU of MoH of Russia
🇷🇺Samara, Russian Federation
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
University Medical Centre Ljubljana
🇸🇮Ljubljana, Slovenia
Hospital Teresa Herrera-Materno Infantil
🇪🇸A Coruña, Spain
Hospital Universitario Son Espases
🇪🇸Palma de Mallorca, Spain
Hospital Universitari Vall d'Hebron (HUVH)
🇪🇸Barcelona, Spain
Kliniska studier i Sverige - Forum Söder
🇸🇪Malmö, Sweden
Universitätsspital Basel
🇨🇭Basel, Switzerland
Karolinska Universitetssjukhuset Solna
🇸🇪Stockholm, Sweden
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Kinderspital Zürich
🇨🇭Zürich, Switzerland
East Kent Hospitals University Foundation Trust, Kent & Canterbury Hospital
🇬🇧Canterbury, United Kingdom
Cambridge University Hospital NHS Foundation Trust, Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Great Ormond Street Hospital for Children NHS Trust
🇬🇧London, United Kingdom
Centro Hospitalar e Universitade de Coimbra
🇵🇹Coimbra, Portugal
Kepler Universitätsklinikum Klinik für Kinder-und Jugendheilkunde
🇦🇹Linz, Austria
Samodzielny Publiczny Dzieciecy Szpital Kliniczny
🇵🇱Warszawa, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1
🇵🇱Gdansk, Poland
FMH Kinder und Jugendmedizin, im Wabern-Zentrum
🇨🇭Wabern, Switzerland
Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, Hampshire, United Kingdom
Laikon General Hospital
🇬🇷Goudi, Athens, Greece
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
General Hospital of Thessaloniki "Ippokratio"
🇬🇷Thessaloniki, Greece
Uniwersytecki Szpital Kliniczny we Wrocławiu
🇵🇱Wroclaw, Poland
Hemoce - Ce
🇧🇷Fortaleza, Ceará, Brazil
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Fundação HEMOPA
🇧🇷Belém, Pará, Brazil
Hemocentro da UNICAMP
🇧🇷Campinas, São Paulo, Brazil
Landes Frauen und Kinderklinik Linz (LFKK Linz)
🇦🇹Linz, Austria
Inselspital Bern
🇨🇭Bern, Switzerland
Luzerner Kantonsspital
🇨🇭Luzern 17, Switzerland
The Moncton City Hospital
🇨🇦Moncton, New Brunswick, Canada
SBHI Chelyabinsk Regional Children's Clinical Hospital
🇷🇺Chelyabinsk, Russian Federation
Centro Hospitalar Lisboa Norte Hospital de Sta. Maria
🇵🇹Lisboa, Portugal
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
South Metropolitan Health Service trading as Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Hemocentro do Espírito Santo
🇧🇷Vitória, Espírito Santo, Brazil
Hospital do Divino Espírito Santo
🇵🇹Ponta Delgada, Açores, Portugal
Azienda Ospedaliera Policlinico Consorziale Di Bari
🇮🇹Bari, Italy
Policlinico S Orsola Malpighi
🇮🇹Bologna, Italy
Ospedale Pugliese -Ciaccio
🇮🇹Catanzaro, Italy
Az. Osp. Univ. Careggi
🇮🇹Firenze, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliera di Padova Clinica Medica II
🇮🇹Padova, Italy
AOUP P. Giaccone
🇮🇹Palermo, Italy
Azienda Ospedaliera Bianchi Melacrino Morelli
🇮🇹Reggio Calabria, Italy
Università degli studi di Roma "La Sapienza"
🇮🇹Roma, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
Policlinico Universitario Gemelli
🇮🇹Roma, Italy
Centro Emofilia e Coagulopatie Rare
🇮🇹Scorrano, Italy
Ospedale Molinette
🇮🇹Torino, Italy
Rigshospitalet
🇩🇰Copenhagen, Denmark
Shenzhen Second People's Hospital
🇨🇳Shenzhen, China
Heim Pál Gyermekkórház
🇭🇺Budapest, Hungary
Hospital Hospital Sant Joan de Déu
🇪🇸Barcelona, Spain
CHRU Purpan CRTH - Pavillon Sénac
🇫🇷Toulouse Cedex 9, France
Hemorgs - Rs
🇧🇷Porto Alegre, Parthenon, Brazil