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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00388674
• Collaborator: (none)
• Enrollment: 12,522
• Locations: 290
• Actual Duration (Months): 118.3
• Patients Per Site: 43.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: entecavir; Drug: Other anti-HBV medication

Study Design

• Study Type: Observational
• Actual Enrollment: 12522 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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
• Actual Study Start Date: Dec 18, 2006
• Actual Primary Completion Date: Oct 26, 2016
• Actual Study Completion Date: Oct 26, 2016

Arms and Interventions

Arm	Intervention/Treatment
A	Drug: entecavir; Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily, Investigator/Patient decision; Other Names: Baraclude BMS-200475
B	Drug: Other anti-HBV medication; Tablets / Oral Solution, Oral, depends on chosen active comparator, depends on chosen active comparator, Investigator/Patient decision

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adjudicated Overall Malignant Neoplasms [10 years]

   The number of participants with Overall Malignant Neoplasm, as adjudicated by Events Adjudication Committee (EAC)

2. Number of Deaths [10 years]

   The number of deaths, as adjudicated by Events Adjudication Committee (EAC)

3. Number of Participants With Liver-related HBV Disease Progression [10 years]

   The number of participants with Liver-related HBV disease progression, as adjudicated by Events Adjudication Committee (EAC)

Secondary Outcome Measures

1. Number of Participants With Non-HCC Malignant Neoplasm [10 years]

   The number of participants with non-HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)

2. Number of Participants With HCC Malignant Neoplasm [10 years]

   The number of participants with HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)

3. Number of Participants With Liver-related Death [10 years]

   The number of participants with Liver-related death, as adjudicated by Events Adjudication Committee (EAC)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scti Research Foundation	Coronado	California	United States	92118
2	Cedars-Sinai Comprehensive Transplant Center	Los Angeles	California	United States	90048
3	Kaiser Permanente Medical Center	San Francisco	California	United States	94118
4	University Of Connecticut Health Center	Farmington	Connecticut	United States	06030-1845
5	University Of Miami Center For Liver Diseases	Miami	Florida	United States	33136
6	Orlando Immunology Center	Orlando	Florida	United States	32803
7	Atlanta Gastroenterology Associates	Atlanta	Georgia	United States	30308
8	Rush University Med Ctr	Chicago	Illinois	United States	60612
9	Indiana University	Indianapolis	Indiana	United States	46202-5121
10	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
11	Medical Procare, Pllc	Flushing	New York	United States	11355
12	Office Of Sing Chan Md	Flushing	New York	United States	11355
13	Beth Israel Medical Center	New York	New York	United States	10003
14	Va New York Harbor Healthcare System	New York	New York	United States	10010
15	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
16	Integris Baptist Medical Center	Oklahoma City	Oklahoma	United States	73112-4481
17	Phgi Associates, Ltd	Philadelphia	Pennsylvania	United States	19106
18	Thomas Jefferson Medical College	Philadelphia	Pennsylvania	United States	19107
19	Upmc Center For Liver Diseases	Pittsburgh	Pennsylvania	United States	15213
20	UT Southwestern Medical Center	Dallas	Texas	United States	7390-8887
21	Local Institution	Ciudad De Buenos Aires	Buenos Aires	Argentina	1155
22	Local Institution	El Palomar	Buenos Aires	Argentina	1684
23	Local Institution	San Salvador De Jujuy	Jujuy	Argentina	Y4600ADE
24	Local Institution	Guaymallen	Mendoza	Argentina	5519
25	Local Institution	Salta	Provincia de Salta	Argentina	A4406CLA
26	Local Institution	Buenos Aires		Argentina	1181
27	Local Institution	Buenos Aires		Argentina	1221
28	Local Institution	Neuquen		Argentina	8300PMB
29	Local Institution	Rio Branco	AC	Brazil	69914-220
30	Local Institution	Manaus	Amazonas	Brazil	69040-000
31	Local Institution	Salvador	Bahia	Brazil	40110-060
32	Local Institution	Salvador	Bahia	Brazil	40110-160
33	Local Institution	Goiania	Goias	Brazil	74605-050
34	Local Institution	Cuiaba	Mato Grosso	Brazil	78048-902
35	Local Institution	Belo Horizonte	Minas Gerais	Brazil	30110-934
36	Local Institution	Belo Horizonte	Minas Gerais	Brazil	30130-100
37	Local Institution	Belo Horizonte	Minas Gerais	Brazil	30150-221
38	Local Institution	Ipatinga	Minas Gerais	Brazil	35160-118
39	Local Institution	Juiz De Fora	Minas Gerais	Brazil	36021-630
40	Local Institution	Curitiba	Parana	Brazil	80240-280
41	Local Institution	Belem	Para	Brazil	66035-080
42	Local Institution	Recife	Pernambuco	Brazil	50100-130
43	Local Institution	Rio De Janeiro / Rj	Rio de Janeiro	Brazil	21041-030
44	Local Institution	Porto Alegres/rs	Rio Grande Do Sul	Brazil	90020-090
45	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
46	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
47	Local Institution	Sao Jose	Santa Catarina	Brazil	88103-400
48	Local Institution	Campinas	Sao Paulo	Brazil	13060-904
49	Local Institution	Campinas	Sao Paulo	Brazil	13083-888
50	Local Institution	Marilia	Sao Paulo	Brazil	17519-000
51	Local Institution	Santo Andre - Sp	Sao Paulo	Brazil	09060-870
52	Local Institution	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15090-000
53	Local Institution	Sorocaba	Sao Paulo	Brazil	18047-600
54	Local Institution	Sao Paulo	SP	Brazil	05403-000
55	Local Institution	Ribeirao Preto		Brazil	14048-900
56	Local Institution	Rio De Janeiro		Brazil	20020
57	Local Institution	Rio De Janeiro		Brazil	20270-004
58	Local Institution	Sao Paulo		Brazil	02128-000
59	Local Institution	Calgary	Alberta	Canada	T2N 4Z6
60	Local Institution	Edmonton	Alberta	Canada	T6G 2E1
61	Local Institution	Vancouver	British Columbia	Canada	V5Z 1H2
62	Local Institution	Toronto	Ontario	Canada	M5G 2C4
63	Local Institution	Montreal	Quebec	Canada	H2X 3J4
64	Local Institution	Hefei	Anhui	China	230022
65	Local Institution	Beijing	Beijing	China	100011
66	Local Institution	Beijing	Beijing	China	100034
67	Local Institution	Beijing	Beijing	China	100039
68	Local Institution	Beijing	Beijing	China	100050
69	Local Institution	Beijing	Beijing	China	100054
70	Local Institution	Chongqing	Chongqing	China	400010
71	Local Institution	Chongqing	Chongqing	China	400038
72	Local Institution	Guangzhou	Guangdong	China	510060
73	Local Institution	Guangzhou	Guangdong	China	510515
74	Local Institution	Shenzhen	Guangdong	China	518114
75	Local Institution	Guiyang	Guizhou	China	550004
76	Local Institution	Haikou	Hainan	China	570311
77	Local Institution	Zhengzhou	Henan	China	450003
78	Local Institution	Zhengzhou	Henan	China	450052
79	Local Institution	Wuhan	Hubei	China	430022
80	Local Institution	Changsha	Hunan	China	410008
81	Local Institution	Changsha	Hunan	China	410011
82	Local Institution	Nanjing	Jiangsu	China	210002
83	Local Institution	Nanjing	Jiangsu	China	210003
84	Local Institution	Nanjing	Jiangsu	China	210029
85	Local Institution	Suzhou	Jiangsu	China	215006
86	Local Institution	Changchun	Jilin	China	130021
87	Local Institution	Dalian	Liaoning	China	116001
88	Local Institution	Shenyang	Liaoning	China	110000
89	Local Institution	Shenyang	Liaoning	China	110004
90	Local Institution	Taiyuan	Shan1xi	China	030001
91	Local Institution	Xi'an	Shan3xi	China	710038
92	Local Institution	Xi'an	Shan3xi	China	710061
93	Local Institution	Jinan	Shandong	China	250021
94	Local Institution	Shanghai	Shanghai	China	200001
95	Local Institution	Shanghai	Shanghai	China	200040
96	Local Institution	Shanghai	Shanghai	China	200083
97	Local Institution	Shanghai	Shanghai	China	200240
98	Local Institution	Shanghai	Shanghai	China	200433
99	Local Institution	Shanghai	Shanghai	China
100	Local Institution	Chengdu	Sichuan	China	610041
101	Local Institution	Tianjin	Tianjin	China	300170
102	Local Institution	Tianjin	Tianjin	China	300192
103	Local Institution	Kunming	Yunnan	China	650032
104	Local Institution	Hangzhou	Zhejiang	China	310003
105	Local Institution	Hangzhou	Zhejiang	China	310014
106	Local Institution	Linhai	Zhejiang	China	317000
107	Local Institution	Ningbo	Zhejiang	China	315010
108	Local Institution	Guangzhou		China	510630
109	Local Institution	ShangHai		China	200025
110	Local Institution	Bogota	Cundinamarca	Colombia
111	Local Institution	Bogota		Colombia
112	Local Institution	Brno		Czechia	625 00
113	Local Institution	Hradec Kralove		Czechia	500 05
114	Local Institution	Ostrava		Czechia	708 52
115	Local Institution	Prague 8		Czechia	180 81
116	Local Institution	Usti Nad Labem		Czechia	400 01
117	Local Institution	Creteil		France	94010
118	Local Institution	Grenoble Cedex 9		France	38043
119	Local Institution	Lille		France	59037
120	Local Institution	Limoges Cedex		France	87042
121	Local Institution	Lyon		France	69004
122	Local Institution	Paris Cedex 14		France	75014
123	Local Institution	Paris Cedex		France	75651
124	Local Institution	Paris		France	75020
125	Local Institution	Vandoeuvre Cedex		France	54511
126	Local Institution	Berlin		Germany	10117
127	Local Institution	Bonn		Germany	53105
128	Local Institution	Dusseldorf		Germany	40225
129	Local Institution	Hamburg		Germany	20099
130	Local Institution	Leipzig		Germany	04103
131	Local Institution	Tuebingen		Germany	72076
132	Local Institution	Wurzburg		Germany	97080
133	Local Institution	Athens	Kolonaki	Greece	10676
134	Local Institution	Alexandroupolis		Greece	68100
135	Local Institution	Athens		Greece	11522
136	Local Institution	Athens		Greece	11527
137	Local Institution	Hyderabad	Andhra Pradesh	India	500012
138	Local Institution	Hyderabad	Andhra Pradesh	India	500034
139	Local Institution	Hyderabad	Andhra Pradesh	India	500068
140	Local Institution	Hyderabad	Andhra Pradesh	India	500082
141	Local Institution	Visakhapatnam	Andhra Pradesh	India	530002
142	Local Institution	Secunderabad	Andhra Pradsh	India	500003
143	Local Institution	Ahemedabad	Gujarat	India	380 006
144	Local Institution	Ahmedabad	Gujarat	India	380006
145	Local Institution	Gurgaon	Haryana	India	122001
146	Local Institution	Bangalore	Karnataka	India	560 054
147	Local Institution	Bangalore	Karnataka	India	560034
148	Local Institution	Mangalore	Karnataka	India	575002
149	Local Institution	Kochi	Kerala	India	682304
150	Local Institution	Bhopal	Madhya Pradesh	India	462016
151	Local Institution	Nagpur	Maharashtra	India	440012
152	Local Institution	Nasik	Maharashtra	India	422002
153	Local Institution	Ludhiana	Punjab	India	141001
154	Local Institution	Jaipur	Rajasthan	India	302017
155	Local Institution	Madurai	Tamil Nadu	India	625002
156	Local Institution	Chennai	Tamilnadu	India	600096
157	Local Institution	Madurai	Tamilnadu	India	625107
158	Local Institution	Lucknow	Uttar Pradesh	India	226014
159	Local Institution	Coimbatore		India	641015
160	Local Institution	Hyderabad		India	500058
161	Local Institution	Indore		India	452014
162	Local Institution	Kolkata		India	700054
163	Local Institution	Ludhiana		India	141008
164	Local Institution	Mumbai		India	400008
165	Local Institution	New Delhi		India	110002
166	Local Institution	Bologna		Italy	40138
167	Local Institution	Napoli		Italy	80131
168	Local Institution	Rome		Italy	00149
169	Local Institution	Ansan-si	Gyeonggi-do	Korea, Republic of	425-707
170	Local Institution	Uijeongbu-Si	Gyeonggi-do	Korea, Republic of	480-717
171	Local Institution	Bucheon		Korea, Republic of	402-767
172	Local Institution	Busan		Korea, Republic of	602-702
173	Local Institution	Busan		Korea, Republic of	602-715
174	Local Institution	Busan		Korea, Republic of	602-739
175	Local Institution	Busan		Korea, Republic of	614-735
176	Local Institution	Chuncheon		Korea, Republic of	200-704
177	Local Institution	Chung-ju		Korea, Republic of	380-060
178	Local Institution	Dae-jeon		Korea, Republic of	301-723
179	Local Institution	Daegu		Korea, Republic of	700-712
180	Local Institution	Daegu		Korea, Republic of	705-718
181	Local Institution	Daejeon City		Korea, Republic of	302-721
182	Local Institution	Gangneung-si		Korea, Republic of	210-711
183	Local Institution	Goyang		Korea, Republic of	411-719
184	Local Institution	Gwangju		Korea, Republic of	503-715
185	Local Institution	Gyeonggi-do		Korea, Republic of	410-769
186	Local Institution	Gyeongju		Korea, Republic of	780-350
187	Local Institution	Incheon		Korea, Republic of	400-711
188	Local Institution	Incheon		Korea, Republic of	405-760
189	Local Institution	Jinju		Korea, Republic of	660-702
190	Local Institution	Koyang City		Korea, Republic of	411-706
191	Local Institution	Seoul		Korea, Republic of	120-749
192	Local Institution	Seoul		Korea, Republic of	130-702
193	Local Institution	Seoul		Korea, Republic of	134-080
194	Local Institution	Seoul		Korea, Republic of	135-710
195	Local Institution	Seoul		Korea, Republic of	135-720
196	Local Institution	Seoul		Korea, Republic of	137-040
197	Local Institution	Seoul		Korea, Republic of	138-736
198	Local Institution	Seoul		Korea, Republic of	140-743
199	Local Institution	Seoul		Korea, Republic of	150-071
200	Local Institution	Seoul		Korea, Republic of	150-713
201	Local Institution	Seoul		Korea, Republic of	152-703
202	Local Institution	Sungnam-si		Korea, Republic of	463-774
203	Local Institution	Sungnam		Korea, Republic of	463-712
204	Local Institution	Suwon-si		Korea, Republic of	442-723
205	Local Institution	Suwon		Korea, Republic of	443-721
206	Local Institution	Ulsan		Korea, Republic of	682-714
207	Local Institution	Wonju		Korea, Republic of	220-701
208	Local Institution	Saltillo	Coahuila	Mexico	25000
209	Local Institution	Guadalajara	Jalisco	Mexico	44160
210	Local Institution	Guadalajara	Jalisco	Mexico	44280
211	Local Institution	Zapopan	Jalisco	Mexico	45116
212	Local Institution	Zapopan	Jalisco	Mexico	45200
213	Local Institution	Cuernavaca	Morelos	Mexico	62170
214	Local Institution	Monterrey, N.l.	Nuevo Leon	Mexico	64460
215	Local Institution	Monterrey	Nuevo Leon	Mexico	64710
216	Local Institution	Culiacan, Sin.	Sinaloa	Mexico	80230
217	Local Institution	Boca Del Rio	Veracruz	Mexico	94298
218	Local Institution	Distrito Federal		Mexico	14080
219	Local Institution	Durango		Mexico	34208
220	Local Institution	Cebu City		Philippines	6000
221	Local Institution	Davao City		Philippines	8000
222	Local Institution	Ermita Manila		Philippines	1000
223	Local Institution	Manila		Philippines	1000
224	Local Institution	Manila		Philippines	1003
225	Local Institution	Metro Manila		Philippines	1500
226	Local Institution	Quezon City		Philippines	1100
227	Local Institution	Krakow		Poland	31-202
228	Local Institution	Krakow		Poland	31-501
229	Local Institution	Lodz		Poland	91-347
230	Local Institution	Poznan		Poland	61-285
231	Local Institution	Raciborz		Poland	47-400
232	Local Institution	Szczecin		Poland	71-455
233	Local Institution	Zawiercie		Poland	42-400
234	Local Institution	Braga		Portugal	4701-965
235	Local Institution	Coimbra		Portugal	3050-075
236	Local Institution	Lisbon		Portugal	1169-050
237	Local Institution	Porto		Portugal	4200-319
238	Local Institution	Bucharest		Romania	020125
239	Local Institution	Bucharest		Romania	021105
240	Local Institution	Bucharest		Romania	022328
241	Local Institution	Bucharest		Romania	030303
242	Local Institution	Bucharest		Romania	050098
243	Local Institution	Constanta		Romania	900591
244	Local Institution	Iasi		Romania	700111
245	Local Institution	Timisoara		Romania	300723
246	Local Institution	Kazan	Tatarstan	Russian Federation	420097
247	Local Institution	Arkhangelsk		Russian Federation	163045
248	Local Institution	Irkutsk		Russian Federation	664047
249	Local Institution	Kirov		Russian Federation	610000
250	Local Institution	Krasnoyarsk		Russian Federation	660014
251	Local Institution	Lipetsk		Russian Federation	398043
252	Local Institution	Moscow		Russian Federation	119021
253	Local Institution	Moscow		Russian Federation	119435
254	Local Institution	Moscow		Russian Federation	125367
255	Local Institution	Nizhniy Novgord		Russian Federation	603076
256	Local Institution	Nizhniy Novgorod		Russian Federation	603022
257	Local Institution	Ryazan		Russian Federation	390005
258	Local Institution	Samara		Russian Federation	430063
259	Local Institution	Yakutsk		Russian Federation	677005
260	Local Institution	Singapore		Singapore	119228
261	Local Institution	Granada		Spain	18012
262	Local Institution	Madrid		Spain	28006
263	Local Institution	Madrid		Spain	28222
264	Local Institution	Oviedo		Spain	33006
265	Local Institution	San Sebastian Guipuzcuoa		Spain	20014
266	Local Institution	Sevilla		Spain	41014
267	Local Institution	Valencia		Spain	46010
268	Local Institution	Kaohsiung		Taiwan	80756
269	Local Institution	Kaohsiung		Taiwan	833
270	Local Institution	Taichung		Taiwan	402
271	Local Institution	Taichung		Taiwan	404
272	Local Institution	Taichung		Taiwan	40705
273	Local Institution	Tainan		Taiwan	70428
274	Local Institution	Taipei		Taiwan	100
275	Local Institution	Taipei		Taiwan	10650
276	Local Institution	Taipei		Taiwan	112
277	Local Institution	Young Kang City		Taiwan	710
278	Local Institution	Hatyai	Songkhla	Thailand	90110
279	Local Institution	Bangkok		Thailand	10330
280	Local Institution	Bangkok		Thailand	10400
281	Local Institution	Bangkok		Thailand	10700
282	Local Institution	Khon Kaen		Thailand	40002
283	Local Institution	Pathumthani		Thailand	12120
284	Local Institution	Adana		Turkey	01330
285	Local Institution	Ankara		Turkey	06100
286	Local Institution	Eskisehir		Turkey	26480
287	Local Institution	Izmir		Turkey	35100
288	Local Institution	Izmir		Turkey	35120
289	Local Institution	Kayseri		Turkey	38039
290	Local Institution	Trabzon		Turkey	61080

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Chair: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00388674
• Other Study ID Numbers: AI463-080
• First Posted: Oct 17, 2006
• Last Update Posted: Jul 30, 2018
• Last Verified: Oct 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bristol-Myers Squibb: Chronic Hepatitis B Virus
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Entecavir

Study Results

Participant Flow

Pre-assignment Detail	Overall, 12,522 participants were enrolled;12,485 participants were randomized; and12,378 participants received treatment. 100 participants were never treated with the study medication; 3 participants were at participant's request; 2 participants were not reported; 1 participant was administrative reason by sponsor; and 1 was other.

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Period Title: Initial Treatment
STARTED	6216	6162
COMPLETED	4388	3576
NOT COMPLETED	1828	2586
Period Title: Initial Treatment
STARTED	6216	6162
COMPLETED	4482	3993
NOT COMPLETED	1734	2169

Baseline Characteristics

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)	Total
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator	Total of all reporting groups
Overall Participants	6216	6162	12378
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.8 (12.11)	39.6 (12.14)	39.7 (12.12)
Sex: Female, Male (Count of Participants)
Female	1503 24.2%	1490 24.2%	2993 24.2%
Male	4713 75.8%	4672 75.8%	9385 75.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 0%	0 0%	3 0%
Not Hispanic or Latino	153 2.5%	154 2.5%	307 2.5%
Unknown or Not Reported	6060 97.5%	6008 97.5%	12068 97.5%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	1 0%	1 0%	2 0%
Asian	5221 84%	5201 84.4%	10422 84.2%
Native Hawaiian or Other Pacific Islander	3 0%	1 0%	4 0%
Black or African American	59 0.9%	68 1.1%	127 1%
White	819 13.2%	780 12.7%	1599 12.9%
Other	113 1.8%	111 1.8%	224 1.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adjudicated Overall Malignant Neoplasms
Description	The number of participants with Overall Malignant Neoplasm, as adjudicated by Events Adjudication Committee (EAC)
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All randomized, treated participants

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Measure Participants	6216	6162
Number [Participants]	331 5.3%	337 5.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entecavir (ETV), Other Anti-HBV Medication (Non-ETV)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3553
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95.03%; 0.800 to 1.084
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio of ETV : Non-ETV Analyses are stratified by geographic region and prior HBV nucleoside/tide experience

2. Primary Outcome

Title	Number of Deaths
Description	The number of deaths, as adjudicated by Events Adjudication Committee (EAC)
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All randomized, treated participants

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Measure Participants	6216	6162
Number [Participants]	238 3.8%	264 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entecavir (ETV), Other Anti-HBV Medication (Non-ETV)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0676
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95.03%; 0.713 to 1.012
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio of ETV : Non-ETV Analyses are stratified by geographic region and prior HBV nucleoside/tide experience

3. Primary Outcome

Title	Number of Participants With Liver-related HBV Disease Progression
Description	The number of participants with Liver-related HBV disease progression, as adjudicated by Events Adjudication Committee (EAC)
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All randomized, treated participants

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Measure Participants	6216	6162
Number [Participants]	350 5.6%	375 6.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entecavir (ETV), Other Anti-HBV Medication (Non-ETV)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1182
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95.03%; 0.769 to 1.030
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio of ETV : Non-ETV Analyses are stratified by geographic region and prior HBV nucleoside/tide experience

4. Secondary Outcome

Title	Number of Participants With Non-HCC Malignant Neoplasm
Description	The number of participants with non-HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All randomized, treated participants

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Measure Participants	6216	6162
Number [Participants]	95 1.5%	81 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entecavir (ETV), Other Anti-HBV Medication (Non-ETV)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.817 to 1.478
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio of ETV : Non-ETV Analyses are stratified by geographic region and prior HBV nucleoside/tide experience

5. Secondary Outcome

Title	Number of Participants With HCC Malignant Neoplasm
Description	The number of participants with HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All randomized, treated participants

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Measure Participants	6216	6162
Number [Participants]	240 3.9%	263 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entecavir (ETV), Other Anti-HBV Medication (Non-ETV)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.727 to 1.032
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio of ETV : Non-ETV Analyses are stratified by geographic region and prior HBV nucleoside/tide experience

6. Secondary Outcome

Title	Number of Participants With Liver-related Death
Description	The number of participants with Liver-related death, as adjudicated by Events Adjudication Committee (EAC)
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All randomized, treated participants

Arm/Group Title	Entecavir (ETV)	Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.	Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
Measure Participants	6216	6162
Number [Participants]	46 0.7%	48 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entecavir (ETV), Other Anti-HBV Medication (Non-ETV)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.608 to 1.365
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio of ETV : Non-ETV Analyses are stratified by geographic region and prior HBV nucleoside/tide experience

Adverse Events

Time Frame	10 years
Adverse Event Reporting Description	Mandatory reporting of non-serious AEs was not required. Reporting of serious adverse events (SAEs) which are considered unrelated (i.e. not likely or not related) to study drug was also not required.
Arm/Group Title	Entecavir (ETV)		Other Anti-HBV Medication (Non-ETV)
Arm/Group Description	Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily.		Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator
All Cause Mortality
	Entecavir (ETV)		Other Anti-HBV Medication (Non-ETV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Entecavir (ETV)		Other Anti-HBV Medication (Non-ETV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/6216 (0.9%)		50/6162 (0.8%)
Gastrointestinal disorders
Ascites	3/6216 (0%)		0/6162 (0%)
Duodenal ulcer haemorrhage	1/6216 (0%)		0/6162 (0%)
Enteritis	1/6216 (0%)		0/6162 (0%)
Gastrointestinal haemorrhage	1/6216 (0%)		0/6162 (0%)
Oesophageal varices haemorrhage	1/6216 (0%)		0/6162 (0%)
Pancreatitis	1/6216 (0%)		0/6162 (0%)
Pancreatitis acute	1/6216 (0%)		0/6162 (0%)
Upper gastrointestinal haemorrhage	6/6216 (0.1%)		0/6162 (0%)
Varices oesophageal	2/6216 (0%)		0/6162 (0%)
General disorders
Chest discomfort	1/6216 (0%)		0/6162 (0%)
Death	1/6216 (0%)		0/6162 (0%)
Electrocution	1/6216 (0%)		0/6162 (0%)
Oedema peripheral	0/6216 (0%)		1/6162 (0%)
Pelvic mass	0/6216 (0%)		1/6162 (0%)
Pyrexia	2/6216 (0%)		0/6162 (0%)
Hepatobiliary disorders
Cholelithiasis	1/6216 (0%)		0/6162 (0%)
Chronic hepatitis	1/6216 (0%)		0/6162 (0%)
Gallbladder polyp	2/6216 (0%)		0/6162 (0%)
Hepatic cirrhosis	4/6216 (0.1%)		0/6162 (0%)
Hepatic fibrosis	1/6216 (0%)		0/6162 (0%)
Hepatic function abnormal	2/6216 (0%)		0/6162 (0%)
Hepatitis	0/6216 (0%)		1/6162 (0%)
Infections and infestations
Appendicitis	2/6216 (0%)		0/6162 (0%)
Chronic hepatitis b	1/6216 (0%)		0/6162 (0%)
Hepatitis b	0/6216 (0%)		1/6162 (0%)
Hepatitis b reactivation	1/6216 (0%)		0/6162 (0%)
Tuberculous pleurisy	1/6216 (0%)		0/6162 (0%)
Injury, poisoning and procedural complications
Atypical femur fracture	0/6216 (0%)		1/6162 (0%)
Foot fracture	1/6216 (0%)		0/6162 (0%)
Multiple fractures	1/6216 (0%)		0/6162 (0%)
Overdose	1/6216 (0%)		0/6162 (0%)
Road traffic accident	1/6216 (0%)		0/6162 (0%)
Toxicity to various agents	0/6216 (0%)		1/6162 (0%)
Investigations
Alanine aminotransferase increased	4/6216 (0.1%)		0/6162 (0%)
Blood bilirubin increased	2/6216 (0%)		0/6162 (0%)
Blood creatine phosphokinase increased	0/6216 (0%)		3/6162 (0%)
Blood creatinine increased	0/6216 (0%)		1/6162 (0%)
Weight decreased	0/6216 (0%)		1/6162 (0%)
Metabolism and nutrition disorders
Hypophosphataemia	0/6216 (0%)		4/6162 (0.1%)
Lactic acidosis	0/6216 (0%)		1/6162 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/6216 (0%)		5/6162 (0.1%)
Myalgia	1/6216 (0%)		1/6162 (0%)
Myopathy	0/6216 (0%)		15/6162 (0.2%)
Myositis	0/6216 (0%)		1/6162 (0%)
Polymyositis	0/6216 (0%)		2/6162 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	8/6216 (0.1%)		0/6162 (0%)
Papillary cystadenoma lymphomatosum	1/6216 (0%)		0/6162 (0%)
Nervous system disorders
Cerebral infarction	1/6216 (0%)		0/6162 (0%)
Coma hepatic	1/6216 (0%)		0/6162 (0%)
Hepatic encephalopathy	1/6216 (0%)		0/6162 (0%)
Hypoaesthesia	0/6216 (0%)		1/6162 (0%)
Mononeuropathy	0/6216 (0%)		1/6162 (0%)
Mononeuropathy multiplex	0/6216 (0%)		1/6162 (0%)
Neuropathy peripheral	0/6216 (0%)		2/6162 (0%)
Psychiatric disorders
Insomnia	1/6216 (0%)		0/6162 (0%)
Renal and urinary disorders
Acute kidney injury	0/6216 (0%)		1/6162 (0%)
Nephropathy	0/6216 (0%)		3/6162 (0%)
Nephropathy toxic	0/6216 (0%)		2/6162 (0%)
Renal impairment	1/6216 (0%)		1/6162 (0%)
Urethral stenosis	1/6216 (0%)		0/6162 (0%)
Other (Not Including Serious) Adverse Events
	Entecavir (ETV)		Other Anti-HBV Medication (Non-ETV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6216 (0%)		0/6162 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.