Efficacy and Durability of Hepatitis A Vaccination in Patients With Advanced Fibrosis and Cirrhosis

Cirrhosis Clinical Trial

Official title:

Efficacy and Durability of Hepatitis A Vaccination in Patients With Advanced Fibrosis and Cirrhosis: A Randomized-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06277882
• Other study ID #: Si 067/2024
• Status: Recruiting
• Phase: Phase 4
• Start date: February 29, 2024
• Est. completion date: May 31, 2025

Study information

• Verified date: March 2024
• Source: Mahidol University
• Contact: Watcharasak Chotiyaputta, Asso Prof
• Phone: 6624197281
• Email: watcharasak.cho[@]mahidol.ac.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The hepatitis A virus (HAV) is a significant global public health concern. The hepatitis A virus is transmitted primarily by the faecal-oral route, leading to acute hepatitis. Symptoms include low-grade fever, anorexia, jaundice, and typically resolve without complications.

However, HAV infection in patients with chronic liver disease, especially those over 50 years old, may result in more severe outcomes, including fulminant hepatitis, with a higher mortality rate compared to the general population

HAV vaccination is a cornerstone of prevention, especially in high-risk groups. Currently, there is a recommendation to vaccinate patients with chronic liver disease against HAV infection. However, these patients often have compromised immune responses, leading to lower vaccine efficacy compared to the general population.

The goal of this randomized controlled trial is to compare the efficacy and safety of the standard 2-dose (0, 6 months) hepatitis A vaccination regimen with an intensive 3-dose (0, 1, 6 months) schedule in patients with advanced fibrosis and cirrhosis.

The main questions it aims to answer are:

• Compared the seroconversion rate of the standard 2-dose (0, 6 months) hepatitis A vaccination regimen versus the intensive 3-dose (0, 1, 6 months) hepatitis A vaccination regimen in patients with advanced fibrosis and cirrhosis.

• Compared the antibody levels against the hepatitis A virus (Anti-HAV IgG) of the standard 2-dose (0, 6 months) hepatitis A vaccination regimen versus the intensive 3-dose (0, 1, 6 months) hepatitis A vaccination regimen in patients with advanced fibrosis and cirrhosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 31, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age = 18 years

• Confirmed advance fibrosis (F3) or cirrhotic (F4) status (radiologic finding or liver stiffness measurement or pathological report)

• Negative anti-HAV IgM, IgG at baseline

Exclusion Criteria:

• Positive anti-HAV IgG at baseline

• Autoimmune hepatitis

• Current hepatocellular carcinoma

• Active other malignancies

• Presence of antibodies against Human Immunodeficiency Virus

• Received immunosuppressive drugs

• Pregnancy or lactation

• Decompensated cirrhosis with MELD = 15

• Chronic illness or bedridden patient who cannot travel to hospital

• Lack of consent to participate in the study

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Hepatitis
• Hepatitis A
• Liver Cirrhosis
• Vaccination

Intervention

Biological:
• HAVRIX
intramuscular injections

Locations

Country	Name	City	State
Thailand	Faculty of Medicine, Siriraj Hospital	Bangkok Noi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (8)

Advisory Committee on Immunization Practices (ACIP); Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 May 19;55 — View Citation

Arguedas MR, McGuire BM, Fallon MB. Implementation of vaccination in patients with cirrhosis. Dig Dis Sci. 2002 Feb;47(2):384-7. doi: 10.1023/a:1013734525348. — View Citation

Ioannou GN. HCC surveillance after SVR in patients with F3/F4 fibrosis. J Hepatol. 2021 Feb;74(2):458-465. doi: 10.1016/j.jhep.2020.10.016. Epub 2020 Dec 7. — View Citation

Keeffe EB. Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases? Am J Gastroenterol. 1995 Feb;90(2):201-5. — View Citation

Lemon SM, Ott JJ, Van Damme P, Shouval D. Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention. J Hepatol. 2017 Sep 5:S0168-8278(17)32278-X. doi: 10.1016/j.jhep.2017.08.034. Online ahead of prin — View Citation

Noor MT, Manoria P. Immune Dysfunction in Cirrhosis. J Clin Transl Hepatol. 2017 Mar 28;5(1):50-58. doi: 10.14218/JCTH.2016.00056. Epub 2017 Mar 10. — View Citation

Webb GW, Kelly S, Dalton HR. Hepatitis A and Hepatitis E: Clinical and Epidemiological Features, Diagnosis, Treatment, and Prevention. Clin Microbiol Newsl. 2020 Nov 1;42(21):171-179. doi: 10.1016/j.clinmicnews.2020.10.001. Epub 2020 Oct 22. — View Citation

Wigg AJ, Wundke R, McCormick R, Muller KR, Ramachandran J, Narayana SK, Woodman RJ. Efficacy of High-Dose, Rapid, Hepatitis A and B Vaccination Schedules in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2019 May;17(6):1210-1212.e1. doi: 10.1016/j.c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-vaccination serological response rate	To compare the seroconversion response rate at month 7; Subjects are considered as being seroconversion if they were initially seronegative and become seropositive	At 7 months after complete vaccine administration
Secondary	Post-vaccination serological response	To compare the seroconversion response rate at month 1; Subjects are considered as being seroconversion if they were initially seronegative and become seropositive	At 30 days after first dose administration
Secondary	Post-vaccination serological response	To compare the seroconversion response rate at 1 year; Subjects are considered as being seroconversion if they were initially seronegative and become seropositive	At 1 year after first dose administration
Secondary	Anti-hepatitis A Virus (HAV) antibody at month 1	To compare Anti-HAV IgG level obtained with two different vaccination schemes against HAV in advance fibrosis and cirrhotic patients	At 30 days after first dose administration
Secondary	Anti-hepatitis A Virus (HAV) antibody at month 7	To compare Anti-HAV IgG level obtained with two different vaccination schemes against HAV in advance fibrosis and cirrhotic patients	At 7 months after complete vaccine administration
Secondary	Anti-hepatitis A Virus (HAV) antibody at 1 year	To compare Anti-HAV IgG level obtained with two different vaccination schemes against HAV in advance fibrosis and cirrhotic patients	At 1 year after first dose administration