A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis

2020 ◽  
Author(s):  
Ivan Fan-Ngai Hung ◽  
Desmond Yat-Hin Yap ◽  
Terence Pok-Siu Yip ◽  
Ricky Ruiqi Zhang ◽  
Kelvin Kai-Wang To ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Hepatitis B Vaccination ◽  
Toll Like Receptor ◽  
Dialysis Patients ◽  
Imiquimod Cream ◽  
Seroprotection Rate ◽  
Double Blind ◽  
Topical Imiquimod

Abstract Background Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients. Methods We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks. Results Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4–2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5–409.3) mIU/mL and 7.2 (2.0–26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16–11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent. Conclusions Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients. Clinical Trials Registration NCT02621112.

scholarly journals P318 Intra-dermal with topical imiquimod pre-treatment versus intra-muscular hepatitis B vaccination in inflammatory bowel disease patients: a double-blind randomized controlled trial

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S344-S345
Author(s):  
K L Ko ◽  
Y F Lam ◽  
K S Cheung ◽  
F N Hung ◽  
W K Leung
Keyword(s):  
Hepatitis B ◽  
Controlled Trial ◽  
Hepatitis B Vaccination ◽  
Recombinant Hepatitis ◽  
Double Blind ◽  
Randomized Controlled ◽  
Topical Imiquimod ◽  
Protection Rate ◽  
Inflammatory Bowel ◽  
Pre Treatment

Abstract Background Patients with inflammatory bowel disease (IBD) are often immunocompromised and at risk of various opportunistic infections including viral hepatitis. Vaccination is recommended to prevent hepatitis B infection, but efficacy with conventional intra-muscular hepatitis B vaccination in IBD patients is suboptimal. Intra-dermal vaccination has been shown to be an effective way in augmenting immune response in poor vaccine responders. In addition, topical imiquimod, a synthetic agonist of toll-like receptor 7, has been shown to further boost the immunogenicity when applied to the injection site before intra-dermal vaccination. Our study compared the efficacy of intra-dermal hepatitis B vaccination with topical imiquimod with conventional intra-muscular hepatitis B vaccination in IBD patients. Methods This is a double-blind, randomized-controlled trial. IBD patients with no evidence of active or past infection nor history of vaccination i.e. negative serology to all HBsAg/Anti-HBc/Anti-HBs were recruited. They were randomized in 1:1 ratio to receive either intra-dermal recombinant hepatitis B vaccine with topical imiquimod pre-treatment to site of injection (ID) or intra-muscular recombinant hepatitis B vaccine with topical aqueous cream (IM). Same dose (20mcg) of vaccine (Engerix B, Glaxo Smith Klein) was administered to both groups at 0, 1, 6 month. The primary outcome was the sero-protection rate at 12-month, defined as percentage of recruited subjects with anti-HBs titre ≥ 10 mIU/mL. Results 104 patients (mean age 46; 68% male; 50% Crohn’s and 50% UC) were enrolled, with 53 received ID and 51 received IM vaccine. The percentage of patients using steroids, immunomulators and biologics at the time of randomization was 15, 55 and 22 %, respectively. Baseline demographic, disease characteristic, and laboratory parameter were comparable between the ID and IM groups. Sero-protection rate at 12-month was significantly higher in the ID arm compared to the IM arm (91% vs. 69%, P=0.005; Figure). Percentage of good responders at 12 month (anti-HBs titre > 100 mIU/mL) was also higher in the ID arm than in the IM (77% vs 59%, P=0.042). Multivariate analysis showed that use of ID vaccine (OR 4.45, 95% CI 1.40-14.47) and a higher albumin level (OR 1.30, 95% CI 1.06-1.58) are associated with better sero-protection rate. There was no significant difference in adverse effects reported in (64% in ID vs 55% in IM; Table). Conclusion ID hepatitis B vaccination with topical imiquimod is safe and offers superior seroprotection against hepatitis B among IBD patients.

scholarly journals 12 Months Persistent Immunogenicity after Hepatitis B Vaccination in Patients with Type 2 Diabetes and Immunogenicity of Revaccination in Non-Responders: An Open-Label Randomized Controlled Trial

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1407
Author(s):  
Bingfeng Han ◽  
Wu Liu ◽  
Juan Du ◽  
Hanyu Liu ◽  
Tianshuo Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Response Rates ◽  
Gansu Province ◽  
Healthy People ◽  
Hepatitis B Vaccination ◽  
Diabetic Patients ◽  
Hepatitis B Vaccines

Background: In initial studies, the immunogenicity and safety of hepatitis B vaccines in patients with diabetes has been assessed in China. Methods: In six township health centers in Gansu Province, 232 diabetic patients and 77 healthy people were allocated to receive two 3-dose hepatitis B vaccines (Group D20SC 0-1-6; Group D20CHO 0-1-6; Group ND20SC 0-1-6). Participants were followed up at 12 months after being fully vaccinated. One dose of the vaccine was randomly administered to non-responders. Chi-square test was used to compare the differences in response rate between two groups. Results: The anti-HBs response rates of three groups decreased from 84.1%, 89.1% and 88.3% at one month to 64.6%, 79.8% and 71.4% at twelve months. There was no statistical difference in the immune response rates between Group D20SC 0-1-6 and Group ND20SC 0-1-6; however, that of Group D20CHO 0-1-6 was higher than that of Group D20SC 0-1-6. After revaccination, the geometric mean concentrations were 491.7 mIU/mL and 29.7 mIU/mL after using vaccines containing 60 μg and 20 μg HBsAg. Conclusions: At 12 months, immune response in diabetic patients were not significantly different from that in healthy people. Revaccination with one dose of hepatitis B vaccine containing 60 μg HBsAg for non-responders was more satisfactory.

scholarly journals Impact and long-term protection of hepatitis B vaccination: 17 years after universal hepatitis B vaccination in Tunisia

2016 ◽  
Vol 144 (16) ◽  
pp. 3365-3375 ◽  
Author(s):  
H. CHAOUCH ◽  
W. HACHFI ◽  
I. FODHA ◽  
O. KALLALA ◽  
S. SAADI ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Geometric Mean ◽  
Tunisian Population ◽  
Hepatitis B Vaccination ◽  
Seroprotection Rate ◽  
Positive Hbsag ◽  
Hbv Vaccination ◽  
Significant Difference ◽  
The Impact

SUMMARYHepatitis B virus (HBV) vaccination has been part of the Expanded Programme of Immunization (EPI) in Tunisia since 1995. The aim of this study was to evaluate, for the first time, the impact of mass vaccination in Tunisia 17 years after this programme was implemented, and in parallel, assess the long-term persistence of anti-HBs antibody in the vaccinated Tunisian population. A total of 1422 students were recruited (703 vaccinated, 719 non-vaccinated). HBV seromarkers were checked. None of the students from either group had positive HBsAg. The overall prevalence of anti-HBc was 0·8%. A Significantly higher prevalence of anti-HBc was noted in unvaccinated students than in vaccinated (1·4% vs. 0·3%, P = 0·02). The overall seroprotection rate (anti-HBs titre ⩾10 mIU/ml) was 68·9% in vaccinated subjects. Seroprotection rates and geometric mean titres decreased significantly with increasing age, reflecting waning anti-HBs titre over time. No significant difference was detected between seroprotection rates and gender or students’ area of origin. Incomplete vaccination was the only factor associated with an anti-HBs titre <10 mIU/ml. This study demonstrates the excellent efficacy of the HBV vaccination programme in Tunisia 17 years after its launch. However, a significant decline of anti-HBs seroprotection has been observed in ⩾15-year-old adolescents which places them at risk of infection. Additional studies are needed in hyperendemic regions in Tunisia.

scholarly journals Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

2020 ◽  
Author(s):  
Elena V Esaulenko ◽  
Aleksey A Yakovlev ◽  
Genady A Volkov ◽  
Anastasia A Sukhoruk ◽  
Kirill G Surkov ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Geometric Mean ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Antigen Vaccine ◽  
Single Antigen ◽  
Antibody Titers ◽  
The Russian Federation ◽  
The Difference ◽  
Mean Concentration

Abstract Background This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. Methods We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: &gt; − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). Results Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was &gt;97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions 3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

scholarly journals Rationale and design for Lowering-hyperUricaemia treatment on cardiovascular outcoMes In peritoNeal diAlysis patients: a prospective, multicentre, double-blind, randomised controlled trial (LUMINA)

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037842
Author(s):  
Wei Chen ◽  
Naya Huang ◽  
Haiping Mao ◽  
Xiao Yang ◽  
Qian Zhou ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Dropout Rate ◽  
Cardiovascular Outcomes ◽  
Control Group ◽  
Type I ◽  
Dialysis Patients ◽  
Double Blind ◽  
Randomised Controlled

IntroductionThe prevalence of hyperuricaemia in peritoneal dialysis patients is quite high. Studies have demonstrated a correlation between hyperuricaemia and cardiovascular disease and treatment of hyperuricaemia reportedly reduces cardiovascular risk in patients with chronic kidney disease. However, whether hyperuricaemia treatment benefits cardiovascular outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is not yet known.Methods and analysesThis prospective, multicentre, double-blind, randomised controlled trial was designed to evaluate the effects of hyperuricaemia treatment on cardiovascular event risk in CAPD patients. Based on a power of 80%, with type I error α=0.05, two-sided test and 1:1 parallel control study, considering a dropout rate of 20%, a total of 548 eligible patients are expected to be randomly assigned to either the hyperuricaemia treatment group (febuxostat) or control group (placebo).Ethics and disseminationThis study has been approved by the Medical Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University and the ethics committees of other participating institutions. Written informed consent will be obtained from potential trial participants or authorised surrogates.The findings of the study will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.Trial registration numberNCT03200210. 25 June 2017. The trial was started on 13 July 2017, and is expected to end by 31 December 2022. Till 20 Jan 2020, a total of 548 patients have been recruited.Protocol versionThe protocol version number and date are YLT-1604-V2.0 and 15 December 2016.

MP680THE EFFECT OF VITAMIN D SUPPLEMENTATION ON RESPONSE TO HEPATITIS B VACCINATION IN DIALYSIS PATIENTS - AN OPEN LABEL PILOT STUDY

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii681-iii681
Author(s):  
Hildegard Hafner-Giessauf ◽  
Sabine Horn ◽  
Hannelore Sprenger-Maehr ◽  
Kathrin Eller ◽  
Alexander Rosenkranz ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pilot Study ◽  
Hepatitis B ◽  
Vitamin D Supplementation ◽  
Hepatitis B Vaccination ◽  
Dialysis Patients ◽  
Open Label
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