Immunogenicity of Hepatitis B Vaccination in Hemodialysis Patients

• Sponsor: Suping Wang (Other)
• Overall Status: Completed
• CT.gov ID: NCT02963714
• Collaborator: Centers for Disease Control and Prevention, China (Other)
• Enrollment: 352
• Arms: 2
• Duration (Months): 43

Study Details

Study Description

Brief Summary

Intramuscular injection of 40 μg hepatitis B vaccine in a standard three-dose schedule or a four-dose schedule is recommended for hemodialysis patients. However, seroconversion rates are inadequate and persistence of immunity remains a challenge.

This is a randomized, controlled trial. The study will evaluate the immunogenicity, immune persistence, and safety of 20 µg and 60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 in hemodialysis patients.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B Vaccine	Biological: 60 µg dose hepatitis B vaccine; Biological: 20 µg dose hepatitis B vaccine	Phase 4

Detailed Description

Participants are randomized in a ratio of 1:1 into 20 µg recombinant hepatitis B vaccine group or 60µg recombinant hepatitis B vaccine group.The 20 µg group will receive three intramuscular injections of the 20 µg recombinant hepatitis B vaccine, while the 60 µg group will receive three intramuscular injections of the 60 µg dose at months 0, 1 and 6, respectively. HBsAg and anti-HBs will be tested during the study period. Adverse reactions will be recorded after vaccination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 352 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Persistence of Intramuscular High Dose Recombinant Hepatitis B Vaccine in Hemodialysis Patients in China: a Multicenter Randomized Controlled Trial
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 60 µg dose hepatitis B vaccine 60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6	Biological: 60 µg dose hepatitis B vaccine; three-dose, 60 µg per dose
Experimental: 20 µg dose hepatitis B vaccine 20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6	Biological: 20 µg dose hepatitis B vaccine; three-dose, 20 µg per dose

Outcome Measures

Primary Outcome Measures

1. Anti-HBs Seroconversion Rate at Month 7 [Month 7]

Secondary Outcome Measures

1. Anti-HBs Seroconversion Rate at Month 42 [Month 42]

2. Anti-HBs Seroconversion Rate at Month 36 [Month 36]

3. Anti-HBs Seroconversion Rate at Month 30 [Month 30]

4. Anti-HBs Seroconversion Rate at Month 24 [Month 24]

5. Anti-HBs Concentration at Month 7 [Month 7]

   Anti-HBs concentration at month 7 as measured by CMIA

6. Anti-HBs Concentration at Month 12 [Month 12]

   Anti-HBs concentration at month 12 as measured by CMIA

7. Anti-HBs Seroconversion Rate at Month 12 [Month 12]

8. Occurrence of Adverse Events After Vaccination [Within 7 days after the vaccination]

   Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine

9. Occurrence of Adverse Events After Vaccination [Within 28 days after the vaccination]

   Occurrence of adverse reactions within 28 days after vaccination with the hepatitis B vaccine

10. Anti-HBs Seroconversion Rate at Month 18 [Month 18]

Other Outcome Measures

1. High-level Response Rate at Month 7 [Month 7]

2. High-level Response Rate at Month 12 [Month 12]

3. High-level Response Rate at Month 18 [Month 18]

4. High-level Response Rate at Month 30 [Month 30]

5. High-level Response Rate at Month 36 [Month 36]

6. High-level Response Rate at Month 42 [Month 42]

7. High-level Response Rate at Month 24 [Month 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Having end-stage renal disease (ESRD) on maintenance hemodialysis

• Aged between 18 and 70 years at enrollment

• Serologically negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) at enrollment

• Willing to adhere to the study protocol

Exclusion Criteria:

• Being pregnant

• Acute cytolysis in the last three months before enrollment

• Any vaccination during the month preceding enrollment

• Intolerance or allergy to any component of the vaccine

• Ongoing opportunistic infection

• Hepatitis C virus infection

• Hematological disorder

• Cancer

• Unexplained fever the week before enrollment

• Immunosuppressive or immunomodulating treatment in the last six months

• Renal transplantation or upcoming renal transplantation

• Liver disease

• Other immunocompromised condition not related to ESRD

• An expected survival of < 6 months

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Suping Wang
• Centers for Disease Control and Prevention, China

Investigators

• Principal Investigator: Suping Wang, Shanxi Medical University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Suping Wang, Professor, Shanxi Medical University
• ClinicalTrials.gov Identifier: NCT02963714
• Other Study ID Numbers: 2012ZX10002001003004001
• First Posted: Nov 15, 2016
• Last Update Posted: Feb 14, 2022
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Suping Wang, Professor, Shanxi Medical University: Hepatitis B, Vaccine; Randomized Controlled Trial; Hemodialysis; Immunogenicity
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Vaccines

Study Results

Participant Flow

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Period Title: Overall Study
STARTED	176	176
COMPLETED	126	126
NOT COMPLETED	50	50

Baseline Characteristics

Arm/Group Title	IM 20μg Group	IM 60μg Group	Total
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Total of all reporting groups
Overall Participants	176	176	352
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.5 (12.2)	45.5 (12.0)	44.5 (12.1)
Sex: Female, Male (Count of Participants)
Female	76 43.2%	88 50%	164 46.6%
Male	100 56.8%	88 50%	188 53.4%
Race/Ethnicity, Customized (Count of Participants)
Han ethnicity	176 100%	175 99.4%	351 99.7%
Hui ethnicity	0 0%	1 0.6%	1 0.3%
Region of Enrollment (Count of Participants)
Urban	89 50.6%	101 57.4%	190 54%
Rural	87 49.4%	75 42.6%	162 46%

Outcome Measures

1. Primary Outcome

Title	Anti-HBs Seroconversion Rate at Month 7
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	141	143
Count of Participants [Participants]	118 67%	132 75%

2. Secondary Outcome

Title	Anti-HBs Seroconversion Rate at Month 42
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	109	102
Count of Participants [Participants]	33 18.8%	40 22.7%

3. Secondary Outcome

Title	Anti-HBs Seroconversion Rate at Month 36
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	115	106
Count of Participants [Participants]	41 23.3%	51 29%

4. Secondary Outcome

Title	Anti-HBs Seroconversion Rate at Month 30
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	118	108
Count of Participants [Participants]	48 27.3%	62 35.2%

5. Secondary Outcome

Title	Anti-HBs Seroconversion Rate at Month 24
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	120	118
Count of Participants [Participants]	54 30.7%	78 44.3%

6. Secondary Outcome

Title	Anti-HBs Concentration at Month 7
Description	Anti-HBs concentration at month 7 as measured by CMIA
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	141	143
Mean (95% Confidence Interval) [mIU/mL]	1488.5	1916.6

7. Secondary Outcome

Title	Anti-HBs Concentration at Month 12
Description	Anti-HBs concentration at month 12 as measured by CMIA
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	126	126
Mean (95% Confidence Interval) [mIU/mL]	407.8	476.2

8. Secondary Outcome

Title	Anti-HBs Seroconversion Rate at Month 12
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	126	126
Count of Participants [Participants]	109 61.9%	114 64.8%

9. Secondary Outcome

Title	Occurrence of Adverse Events After Vaccination
Description	Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine
Time Frame	Within 7 days after the vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	174	175
Count of Participants [Participants]	14 8%	14 8%

10. Secondary Outcome

Title	Occurrence of Adverse Events After Vaccination
Description	Occurrence of adverse reactions within 28 days after vaccination with the hepatitis B vaccine
Time Frame	Within 28 days after the vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	174	175
Count of Participants [Participants]	7 4%	8 4.5%

11. Secondary Outcome

Title	Anti-HBs Seroconversion Rate at Month 18
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	127	126
Count of Participants [Participants]	77 43.8%	96 54.5%

12. Other Pre-specified Outcome

Title	High-level Response Rate at Month 7
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	141	143
Count of Participants [Participants]	88 50%	107 60.8%

13. Other Pre-specified Outcome

Title	High-level Response Rate at Month 12
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	126	126
Count of Participants [Participants]	67 38.1%	82 46.6%

14. Other Pre-specified Outcome

Title	High-level Response Rate at Month 18
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	127	126
Count of Participants [Participants]	30 17%	38 21.6%

15. Other Pre-specified Outcome

Title	High-level Response Rate at Month 30
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	118	108
Count of Participants [Participants]	15 8.5%	19 10.8%

16. Other Pre-specified Outcome

Title	High-level Response Rate at Month 36
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	115	106
Count of Participants [Participants]	14 8%	14 8%

17. Other Pre-specified Outcome

Title	High-level Response Rate at Month 42
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	109	102
Count of Participants [Participants]	8 4.5%	10 5.7%

18. Other Pre-specified Outcome

Title	High-level Response Rate at Month 24
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM 20μg Group	IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.	Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
Measure Participants	120	118
Count of Participants [Participants]	19 10.8%	23 13.1%

Adverse Events

Arm/Group Title	IM 20μg Group		IM 60μg Group
Arm/Group Description	Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6.		Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6.
All Cause Mortality
	IM 20μg Group		IM 60μg Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/174 (0%)		0/175 (0%)
Serious Adverse Events
	IM 20μg Group		IM 60μg Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/174 (0%)		0/175 (0%)
Other (Not Including Serious) Adverse Events
	IM 20μg Group		IM 60μg Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/174 (4.6%)		8/175 (4.6%)
Musculoskeletal and connective tissue disorders
pain	8/174 (4.6%)		8/175 (4.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.