Safety and Pregnancy Outcomes in Thrombocythemia Patients Exposed to XAGRID® (Anagrelide Hydrochloride) Compared to Other Treatments

Thrombocythemia, Essential Clinical Trial

Official title:

A Non-Interventional, Post Authorisation Safety Study, to Continuously Monitor Safety and Pregnancy Outcomes in a Cohort of At-Risk Essential Thrombocythaemia (ET) Subjects Exposed to Xagrid Compared to Other Conventional Cytoreductive Treatments

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00567502
• Other study ID #: SPD422-401
• Status: Completed
• Start date: May 31, 2005
• Est. completion date: April 30, 2014

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational safety study being conducted in Europe comparing patients taking Xagrid to patients taking other cytoreductive treatments. The plan is to enrol at least 750 subjects taking Xagrid with up to 3000 subjects taking other cytoreductive therapies. The study will collect follow up data for 5 years for each patient enrolled that will focus on collecting data related to pre-defined events (PDEs) and Suspected Serious Adverse Reactions (SSARs).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3647
• Est. completion date: April 30, 2014
• Est. primary completion date: April 30, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• High risk ET patients

• Subjects who can give written informed consent.

• Subjects taking cytoreductive therapy

Exclusion Criteria:

• Contraindications listed by the product being used.

• Patient cannot be participating in another clinical trial.

Related Conditions & MeSH terms

• Thrombocythemia, Essential
• Thrombocytosis

Locations

Country	Name	City	State
Cyprus	Clinic of Haematology	Limassol
Denmark	Rigshospitalet	Copenhagen
Denmark	SUS-Esbjerg Maematologisk afdelning	Esbjerg
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Denmark	Roskilde Sygehus	Roskilde
Denmark	Vejle Sygehus	Vejle
Denmark	Viborg Hospital	Viborg
Finland	Helsinki University Hospital	Helsinki
Finland	Jyvaskyla Central Hospital	Jyvaskyla
Finland	Kuopio University Hospital	Kuopio
France	Centre Hospitalier Victor Dupouy	Argenteuil Cedex
France	Centre Hospitalier de Beauvais	Beauvais
France	Hopital Avicenne	Bobigny
France	Hopital de la Cavale Blanche	Brest Cedex
France	CHU Clemenceau	Caen cedex
France	Hopital Henri Mondor	Creteil
France	Cabinet Medical	Dijon
France	Hopital Simone Veil	Eaubonne
France	CHU de Grenoble Hopital Albert Michallon	Grenoble Cedex 09
France	Centre Hospitalier de Lens	Lens
France	CHRU de Lille - Hopital Claude Huriez	Lille cedex
France	Hopital Saint Vincent de Paul	Lille cedex
France	CHU de Limoges - Hopital Universitaire Dupuytren	Limoges Cedex
France	Centre Leon-Berard	Lyon
France	Hopital Nord	Marseille
France	C.H.U. de Nice Hopital de l Archet 1	Nice
France	Hopital Pitie Salpetriere	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Lariboisiere	Paris Cedex 10
France	Hopital Hotel Dieu	Paris Cedex 4
France	Hopital Haut Leveque - CHU de Bordeaux	Pessac
Germany	Studienzentrum	Aschaffenburg
Germany	Praxis Dr. Heinrich, Dr. Brudler, Dr. Bangerter	Augsburg
Germany	Hamatologisch-Onkologische Praxis	Dresden
Germany	Praxis Dr. Weniger und Dr. Bittrich	Erfurt
Germany	Onkologische Gemeinschaftspraxis	Frankfurt/Main
Germany	IORC GmbH	Hamburg
Germany	Internistische Praxis	Hornberg
Germany	Universitatsklinikum Koeln	Koeln
Germany	Praxis Schmitz and Steinmetz	Koln
Germany	Gemeinschaftspraxis fur Hamatologie und Internistische Onkologie	Magdeburg
Germany	Hamatologisch-Onkologische Praxis	Moers
Germany	Praxis Dr. Schick	Muenchen
Germany	Hamatologisch-Onkologische Gemeinschaftspraxis	Muenster
Germany	Ambulante Chemotherapie	Munchen
Germany	Hamato-Onkologische Schwerpunktpraxis	Munich
Germany	Praxis und Tagesklinik fur Internistische Onkologie	Recklinghausen
Germany	Caritasklinik St. Theresia	Saarbruecken
Germany	Schwerpunktpraxis fur Hamatologie und Internistische Onkologie	Saarbruecken
Germany	Universitatsklinik Ulm	Ulm
Germany	Hamatologie und Onkologie	Weiden
Germany	Praxis Dr. med. Yolanda Rodemer	Wilhelmshaven
Greece	3rd Hospital of IKA	Athens
Greece	401 General Army Hospital	Athens
Greece	General Hospital of Athens	Athens
Greece	General Hospital of Athens G.Gennimatas	Athens
Greece	General Hospital of Athens Hippocratio	Athens
Greece	General Hospital of Athens Laiko	Athens
Greece	Henry Dunant Hospital	Athens
Greece	Hygeia Hospital	Athens
Greece	Laikon General Hospital of Athens	Athens
Greece	Metropolitan Hospital	Athens
Greece	University Hospital of Athens ¿Attikon¿	Athens
Greece	University Hospital of Athens Attikon	Athens
Greece	University Hospital of Heraklion	Heraklion
Greece	University Hospital of Ioannina	Ioannina
Greece	University General Hospital of Larissa	Larissa
Greece	Makarios Hospital	Nicchia
Greece	St. Andrews General Hospital of Patra	Patra
Greece	University Hospital of Patra	Patras
Greece	General Hospital of Thessaioniki	Thessaloniki
Greece	Ippokration Hospital D Clinic of Internal Medicine	Thessaloniki
Greece	Papageorgiou Hospital	Thessaloniki
Ireland	Midland Regional Hospital	Tullamore
Italy	Ospedale Le Torrette	Ancona
Italy	Ospedale Arezzo	Arezzo
Italy	Ospedale Policlinico Consorziale	Bari
Italy	A.O. Spedali Civili di Brescia	Brescia
Italy	Presidio Ospedaliero Perrino	Brindisi
Italy	Ospedale Ferrarotto	Catania
Italy	Ospedale Civile	Civitanova Marche
Italy	Ospedale Santa Croce	Fano
Italy	Ospedale Careggi	Florence
Italy	Azienda Ospedaliera Ospedali Riuniti Foggia	Foggia
Italy	Ospedale S. Martino	Genova
Italy	Ospedale S.Martino	Genova
Italy	Ospedale San Martino	Genova
Italy	Ospedale San salvatore	L'Aquila
Italy	Ospedale Umberto I	Mestre
Italy	Policlinico	Modena
Italy	Azienda ospedaliera S. Gerardo	Monza
Italy	Ospedale A.Cardarelli	Napoli
Italy	Ospedale Cardarelli	Napoli
Italy	Universita Federico II	Napoli
Italy	Ospedale Maggiore della Carita	Novara
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Ospedale Maggiore	Parma
Italy	IRCCS Policlinico S. Matteo	Pavia
Italy	Policlinico Monteluce	Perugia
Italy	Ospedale S. Salvatore	Pesaro
Italy	Ospedale Civile	Piacenza
Italy	Ospedale civile	Ragusa
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	San camillo de Lellis	Rieti
Italy	Ospedale oncologico regionale	Rionero in Vulture
Italy	Policlinico Gemelli	Roma
Italy	Ospedale Nuova Regina Margherita	Rome
Italy	Ospedale S.Spirito	Rome
Italy	Ospedale Umberto I	Rome
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	Padiglione ex-oncologico Ospedale S.Maria	Terni
Italy	Ospedale Luigi Gonzaga	Torino
Italy	Ospedale Molinette	Torino
Italy	Ospedale civile	Vigevano
Netherlands	VU medical Center Amsterdam	Amsterdam
Norway	Sykehuset Ostfold	Fredrikstad
Norway	Universitetssykehuset Nord-Norge Hf	Tromso
Norway	Akershus University Hospital	Viken
Portugal	Servico de Hematologia	Vila Nova de Gaia
Spain	Hospital San Eloy	Barakaldo
Spain	Hospital del Mar	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Josep Trueta	Gerona
Spain	Complexo Hospitalario Xeral Calde	Lugo
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital U. 12 de Octubre	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital JM Morales Meseguer	Murcia
Spain	Hospital Clinico Universitario Salamanca	Salamanca
Spain	Hospital Universitario de Canarias	Santa Cruz de Tenerife
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Clinico Universitario Valencia	Valencia
Sweden	Falu Lasarett	Falun
Sweden	Medicine Clinic	Gavle
Sweden	Lanssjukhuset Ryhov	Jonkoping
Sweden	Ljungby Hospital Medical Clinic	Ljungby
Sweden	University Hospital MAS	Malmo
Sweden	University Hospital	Orebro
Sweden	Karolinska University Hospital	Stockholm
Sweden	Sodersjukhuset - Medicinkliniken	Stockholm
Sweden	Lanssjukhuset Sundsvall - Harnosand	Sundsvall
Sweden	Uddevalla Hospital	Uddevalla
Sweden	Akademiska Hospital Uppsala	Uppsala
Sweden	Centrallasarettet - Medicinavdelningen	Vasteras
United Kingdom	Royal United Hospital	Bath
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Avon Haematology Unit BHOC	Bristol
United Kingdom	Darlington Memorial Hospital	Darlington
United Kingdom	Doncaster Royal Infirmary	Doncaster
United Kingdom	Georgina Oncology Unit	Dudley
United Kingdom	James Paget University Hospital	Great Yarmouth
United Kingdom	Hull Royal Infirmary	Hull
United Kingdom	Guy's and Thomas' NHS Foundation Trust	London
United Kingdom	North Tyneside General Hospital	North Shields
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

Cyprus,  Denmark,  Finland,  France,  Germany,  Greece,  Ireland,  Italy,  Netherlands,  Norway,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies	Pre-defined events (PDEs) were evaluated whenever an event occurred and was defined by a panel of independent qualified physicians, blinded to cytoreductive therapy, validated all PDEs prior to analysis (Event Validation Panel). Non-PDE death only included deaths not recorded as outcome of another PDE.	Up to 5 years
Primary	Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events	SSAR: serious adverse event (SAE) that was considered related to cytoreductive therapy. SAE: any untoward medical occurrence that at any dose resulted in death, life-threatening (at the time of the event), in-patient hospitalization/prolongation of existing hospitalization (elective hospitalizations/procedures for pre-existing conditions that had not worsened were excluded), resulted in persistent or significant disability/incapacity or congenital abnormality/birth defect. Relatedness (suspected/not suspected) to XAGRID or other cytoreductive theraphy was determined by the investigator. As for SSARs, it was important to consider whether the events were related to XAGRID or other cytoreductive therapy. A participant was included in Xagrid or other treatment group based on treatment exposure, participants received Xagrid + Other was counted both in Xagrid and other treatment group.	Up to 5 years
Secondary	Event Rate of Thrombohaemorrhagic Events	Event Rate of Thrombohaemorrhagic Events was calculated by dividing number of participants with events by total patient-year exposure. The reporting unit is per 100 participant-years of treatment exposure. Thrombohaemorrhagic Events is a composite endpoint of the PDEs myocardial infarction, angina, stroke, transient ischaemic attack, venous thromboembolic events, intermittent claudication/digital ischaemia, and major haemorrhagic events.	Up to 5 years
Secondary	Platelet Count		Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60
Secondary	Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy	Total duration for each participant = sum of [stop date - start date + 1] across all periods of time where the specific treatment was taken during the study, where start date = registration/consent date for treatments started before registration/consent date and/or stop date withdrawal/final date for treatments ongoing at the time of withdrawal/end of study. Where a participant has multiple records of the same therapy on the same day, the therapy is counted once for that day.	Up to 5 years
Secondary	Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy	Since the study is observational nature, interpreting the table is difficult due to inconsistencies in reporting the units of the dose.	Up to 5 years