Study of Entecavir in Patients With Chronic Hepatitis B Virus (HBV) Infection

Chronic Hepatitis B Clinical Trial

Official title:

Randomized, Observational Study of Entecavir to Assess Long-term Outcomes Associated With Nucleoside/Nucleotide Monotherapy for Patients With Chronic HBV Infection: The REALM Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00388674
• Other study ID #: AI463-080
• Status: Completed
• Start date: December 18, 2006
• Est. completion date: October 26, 2016

Study information

• Verified date: October 2017
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to prospectively assess the long-term outcomes (benefits and risks) associated with entecavir (ETV) therapy as compared to other antivirals approved for the treatment of chronic HBV infection. For the China substudy, patients randomized to entecavir will have safety and efficacy assessments performed during the first year of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12522
• Est. completion date: October 26, 2016
• Est. primary completion date: October 26, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Chronic HBV infection

• HBV nucleoside/tide-naive or -experienced

• Patients who, in opinion of investigator, are appropriate for initiating or modifying their HBV therapy and who are appropriate for a treatment regimen comprised of nucleoside/tide monotherapy with either ETV or another standard of care HBV nucleoside/tide analogue

• Age 16 and older or minimum age required in a given country

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Patients who, in the opinion of the investigator, are expected to have a liver transplant-free survival of less than one year

• Patients who, in the opinion of the investigator, are virologically controlled on their current treatment regimen and clinically responding to treatment, unless the regimen needs to be modified for medication intolerance

• Coinfection with HIV

• History of malignant neoplasm(s), including hepatocellular carcinoma (HCC) and carcinoma in situ (CIS), but excluding non-melanoma skin cancers

• Patients with chronic renal insufficiency, defined as a creatinine clearance < 50 ml/min who do not have either of the following means of dose reducing ETV:

i. an approved country-specific ETV label which includes the extended interval ETV dose modification method and/or ii. an approved country specific label for the ETV oral solution AND access to the oral solution

• History of dysplastic liver nodules

• Known history of allergy to nucleoside/tide analogues

• Prior or current treatment with entecavir

• An investigator proposed study regimen which will include only interferon-alfa

• An investigator proposed study regimen of combination (two or more) HBV nucleoside/tide analogues

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• entecavir
Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily, Investigator/Patient decision
• Other anti-HBV medication
Tablets / Oral Solution, Oral, depends on chosen active comparator, depends on chosen active comparator, Investigator/Patient decision

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Ciudad De Buenos Aires	Buenos Aires
Argentina	Local Institution	El Palomar	Buenos Aires
Argentina	Local Institution	Guaymallen	Mendoza
Argentina	Local Institution	Neuquen
Argentina	Local Institution	Salta	Provincia de Salta
Argentina	Local Institution	San Salvador De Jujuy	Jujuy
Brazil	Local Institution	Belem	Para
Brazil	Local Institution	Belo Horizonte	Minas Gerais
Brazil	Local Institution	Belo Horizonte	Minas Gerais
Brazil	Local Institution	Belo Horizonte	Minas Gerais
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Cuiaba	Mato Grosso
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Ipatinga	Minas Gerais
Brazil	Local Institution	Juiz De Fora	Minas Gerais
Brazil	Local Institution	Manaus	Amazonas
Brazil	Local Institution	Marilia	Sao Paulo
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegres/rs	Rio Grande Do Sul
Brazil	Local Institution	Recife	Pernambuco
Brazil	Local Institution	Ribeirao Preto
Brazil	Local Institution	Rio Branco	AC
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Rio De Janeiro / Rj	Rio de Janeiro
Brazil	Local Institution	Salvador	Bahia
Brazil	Local Institution	Salvador	Bahia
Brazil	Local Institution	Santo Andre - Sp	Sao Paulo
Brazil	Local Institution	Sao Jose	Santa Catarina
Brazil	Local Institution	Sao Jose Do Rio Preto	Sao Paulo
Brazil	Local Institution	Sao Paulo	SP
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sorocaba	Sao Paulo
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Vancouver	British Columbia
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Changchun	Jilin
China	Local Institution	Changsha	Hunan
China	Local Institution	Changsha	Hunan
China	Local Institution	Chengdu	Sichuan
China	Local Institution	Chongqing	Chongqing
China	Local Institution	Chongqing	Chongqing
China	Local Institution	Dalian	Liaoning
China	Local Institution	Guangzhou
China	Local Institution	Guangzhou	Guangdong
China	Local Institution	Guangzhou	Guangdong
China	Local Institution	Guiyang	Guizhou
China	Local Institution	Haikou	Hainan
China	Local Institution	Hangzhou	Zhejiang
China	Local Institution	Hangzhou	Zhejiang
China	Local Institution	Hefei	Anhui
China	Local Institution	Jinan	Shandong
China	Local Institution	Kunming	Yunnan
China	Local Institution	Linhai	Zhejiang
China	Local Institution	Nanjing	Jiangsu
China	Local Institution	Nanjing	Jiangsu
China	Local Institution	Nanjing	Jiangsu
China	Local Institution	Ningbo	Zhejiang
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	ShangHai
China	Local Institution	Shenyang	Liaoning
China	Local Institution	Shenyang	Liaoning
China	Local Institution	Shenzhen	Guangdong
China	Local Institution	Suzhou	Jiangsu
China	Local Institution	Taiyuan	Shan1xi
China	Local Institution	Tianjin	Tianjin
China	Local Institution	Tianjin	Tianjin
China	Local Institution	Wuhan	Hubei
China	Local Institution	Xi'an	Shan3xi
China	Local Institution	Xi'an	Shan3xi
China	Local Institution	Zhengzhou	Henan
China	Local Institution	Zhengzhou	Henan
Colombia	Local Institution	Bogota	Cundinamarca
Colombia	Local Institution	Bogota
Czechia	Local Institution	Brno
Czechia	Local Institution	Hradec Kralove
Czechia	Local Institution	Ostrava
Czechia	Local Institution	Prague 8
Czechia	Local Institution	Usti Nad Labem
France	Local Institution	Creteil
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Lille
France	Local Institution	Limoges Cedex
France	Local Institution	Lyon
France	Local Institution	Paris
France	Local Institution	Paris Cedex
France	Local Institution	Paris Cedex 14
France	Local Institution	Vandoeuvre Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Bonn
Germany	Local Institution	Dusseldorf
Germany	Local Institution	Hamburg
Germany	Local Institution	Leipzig
Germany	Local Institution	Tuebingen
Germany	Local Institution	Wurzburg
Greece	Local Institution	Alexandroupolis
Greece	Local Institution	Athens
Greece	Local Institution	Athens
Greece	Local Institution	Athens	Kolonaki
India	Local Institution	Ahemedabad	Gujarat
India	Local Institution	Ahmedabad	Gujarat
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bhopal	Madhya Pradesh
India	Local Institution	Chennai	Tamilnadu
India	Local Institution	Coimbatore
India	Local Institution	Gurgaon	Haryana
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Hyderabad
India	Local Institution	Indore
India	Local Institution	Jaipur	Rajasthan
India	Local Institution	Kochi	Kerala
India	Local Institution	Kolkata
India	Local Institution	Lucknow	Uttar Pradesh
India	Local Institution	Ludhiana	Punjab
India	Local Institution	Ludhiana
India	Local Institution	Madurai	Tamil Nadu
India	Local Institution	Madurai	Tamilnadu
India	Local Institution	Mangalore	Karnataka
India	Local Institution	Mumbai
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	Nasik	Maharashtra
India	Local Institution	New Delhi
India	Local Institution	Secunderabad	Andhra Pradsh
India	Local Institution	Visakhapatnam	Andhra Pradesh
Italy	Local Institution	Bologna
Italy	Local Institution	Napoli
Italy	Local Institution	Rome
Korea, Republic of	Local Institution	Ansan-si	Gyeonggi-do
Korea, Republic of	Local Institution	Bucheon
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Chuncheon
Korea, Republic of	Local Institution	Chung-ju
Korea, Republic of	Local Institution	Dae-jeon
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Daejeon City
Korea, Republic of	Local Institution	Gangneung-si
Korea, Republic of	Local Institution	Goyang
Korea, Republic of	Local Institution	Gwangju
Korea, Republic of	Local Institution	Gyeonggi-do
Korea, Republic of	Local Institution	Gyeongju
Korea, Republic of	Local Institution	Incheon
Korea, Republic of	Local Institution	Incheon
Korea, Republic of	Local Institution	Jinju
Korea, Republic of	Local Institution	Koyang City
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Sungnam
Korea, Republic of	Local Institution	Sungnam-si
Korea, Republic of	Local Institution	Suwon
Korea, Republic of	Local Institution	Suwon-si
Korea, Republic of	Local Institution	Uijeongbu-Si	Gyeonggi-do
Korea, Republic of	Local Institution	Ulsan
Korea, Republic of	Local Institution	Wonju
Mexico	Local Institution	Boca Del Rio	Veracruz
Mexico	Local Institution	Cuernavaca	Morelos
Mexico	Local Institution	Culiacan, Sin.	Sinaloa
Mexico	Local Institution	Distrito Federal
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey, N.l.	Nuevo Leon
Mexico	Local Institution	Saltillo	Coahuila
Mexico	Local Institution	Zapopan	Jalisco
Mexico	Local Institution	Zapopan	Jalisco
Philippines	Local Institution	Cebu City
Philippines	Local Institution	Davao City
Philippines	Local Institution	Ermita Manila
Philippines	Local Institution	Manila
Philippines	Local Institution	Manila
Philippines	Local Institution	Metro Manila
Philippines	Local Institution	Quezon City
Poland	Local Institution	Krakow
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Poznan
Poland	Local Institution	Raciborz
Poland	Local Institution	Szczecin
Poland	Local Institution	Zawiercie
Portugal	Local Institution	Braga
Portugal	Local Institution	Coimbra
Portugal	Local Institution	Lisbon
Portugal	Local Institution	Porto
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucharest
Romania	Local Institution	Constanta
Romania	Local Institution	Iasi
Romania	Local Institution	Timisoara
Russian Federation	Local Institution	Arkhangelsk
Russian Federation	Local Institution	Irkutsk
Russian Federation	Local Institution	Kazan	Tatarstan
Russian Federation	Local Institution	Kirov
Russian Federation	Local Institution	Krasnoyarsk
Russian Federation	Local Institution	Lipetsk
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Nizhniy Novgord
Russian Federation	Local Institution	Nizhniy Novgorod
Russian Federation	Local Institution	Ryazan
Russian Federation	Local Institution	Samara
Russian Federation	Local Institution	Yakutsk
Singapore	Local Institution	Singapore
Spain	Local Institution	Granada
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Oviedo
Spain	Local Institution	San Sebastian Guipuzcuoa
Spain	Local Institution	Sevilla
Spain	Local Institution	Valencia
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Tainan
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Young Kang City
Thailand	Local Institution	Bangkok
Thailand	Local Institution	Bangkok
Thailand	Local Institution	Bangkok
Thailand	Local Institution	Hatyai	Songkhla
Thailand	Local Institution	Khon Kaen
Thailand	Local Institution	Pathumthani
Turkey	Local Institution	Adana
Turkey	Local Institution	Ankara
Turkey	Local Institution	Eskisehir
Turkey	Local Institution	Izmir
Turkey	Local Institution	Izmir
Turkey	Local Institution	Kayseri
Turkey	Local Institution	Trabzon
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Rush University Med Ctr	Chicago	Illinois
United States	Scti Research Foundation	Coronado	California
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University Of Connecticut Health Center	Farmington	Connecticut
United States	Medical Procare, Pllc	Flushing	New York
United States	Office Of Sing Chan Md	Flushing	New York
United States	Indiana University	Indianapolis	Indiana
United States	Cedars-Sinai Comprehensive Transplant Center	Los Angeles	California
United States	University Of Miami Center For Liver Diseases	Miami	Florida
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Va New York Harbor Healthcare System	New York	New York
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	Orlando Immunology Center	Orlando	Florida
United States	Phgi Associates, Ltd	Philadelphia	Pennsylvania
United States	Thomas Jefferson Medical College	Philadelphia	Pennsylvania
United States	Upmc Center For Liver Diseases	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  India,  Italy,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adjudicated Overall Malignant Neoplasms	The number of participants with Overall Malignant Neoplasm, as adjudicated by Events Adjudication Committee (EAC)	10 years
Primary	Number of Deaths	The number of deaths, as adjudicated by Events Adjudication Committee (EAC)	10 years
Primary	Number of Participants With Liver-related HBV Disease Progression	The number of participants with Liver-related HBV disease progression, as adjudicated by Events Adjudication Committee (EAC)	10 years
Secondary	Number of Participants With Non-HCC Malignant Neoplasm	The number of participants with non-HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)	10 years
Secondary	Number of Participants With HCC Malignant Neoplasm	The number of participants with HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)	10 years
Secondary	Number of Participants With Liver-related Death	The number of participants with Liver-related death, as adjudicated by Events Adjudication Committee (EAC)	10 years

External Links

•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form