Ignite Creation Date:
2024-05-06 @ 3:18 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04588077
Status:
RECRUITING
Last Update Posted:
2024-03-13
First Post:
2020-09-18
Brief Title:
Comparison Between 2-dose Versus 3-dose Regimens of Heplisav B in Cirrhosis
Sponsor:
Mercy Medical Center
Organization:
Mercy Medical Center
Study Overview
Official Title:
Comparison the Seroconversion Rate Between Two-dose and Three-dose Regimens of Heplisav B Among Patients With Cirrhosis a Randomized-control Prospective Study
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Investigators want to compare the seroconversion rates between two-dose and three-dose regimens of the hepatitis B vaccine Heplisav B among patients with cirrhosis a randomized prospective study
Detailed Description:
Study Rationale
Hepatitis B virus is a major cause of acute and chronic liver disease both in the United States and worldwide In 2016 an estimated 862000 people were living with HBV infection in the US with a total of 1649 US death certificates recorded as an underlying or contributing cause of death Chronic infection may cause liver cirrhosis and hepatocellular carcinoma HCC Since the introduction of the vaccine in the 1990s there has been a significant decline in the incidence of HBV infection Approved in November 2017 Heplisav-B uses a synthetic cytosine phosphoguanine oligonucleotide derived from bacterial DNA it is thought to stimulate the immune system through activation of the toll-like receptor 9 pathway which induces the production of cytokines such as interleukines such as interleukine-12 and interferon-alpha It has been shown to induce higher immunity in healthy individuals compared to conventional vaccines
The HBsAb titer should be checked 8 to 12 weeks after the administration of the vaccination series Good responders were defined as those having the anti-HBs titer were 100 mUIml poor responders having anti-HBs titer between 10 and 99 mUIml and nonresponders having anti-HBs titer 10 mIUml The Seroprotection rate by age group in the healthy population is 100 in the 18-29-year-old group 989 in the 30-29 -year-old group 972 in the 40-49-year-old group 952 in the 50-59-year-old group 916 in 60-70-year-old group However 5 of the general population will not mount a protection response
Response to HBV vaccine is variable among patients with chronic diseases such as HIV infection celiac disease IBD end-stage renal disease diabetes The immunogenicity of the hepatitis B vaccine is also lower in decompensated cirrhosis Among cirrhotic patients only 45 who received Heplisav-B achieved immunity in investigators previous retrospective analysis The usual approach to HBV vaccine nonresponse is repeating the vaccine series in noninfected individuals
Investigational Plan
Study Design Duration Patients with cirrhosis or chronic liver disease presented to the hepatology clinic in Mercy Medical Center between 092020 and 072021 who do not have immunity against Hepatitis B defined as anti-HBs titer 10 mIUml will be recruited Patients will be stratified based on cirrhosis vs no-cirrhosis and vaccine naive vs vaccine experienced Patients who had more than one vaccination series will not be included Previous vaccination could be either Heplisav or Engerix however this information will be collected The investigators plan is to do the 1st part of the study is in treatment-naive patients and expand it to vaccine experienced
Investigators will randomize patients to receive Heplisav-B in 0 4 weeks or Heplisav-B in 0 4 8 weeks The HBV surface antibody titer will be checked 8 to 12 weeks after administration of the vaccination series and classified into good responders poor responders and nonresponders based on antibody titers
Investigators will collect basic data including age MELD scores etiologies of cirrhosis non-alcoholic fatty liver disease hepatitis C alcohol-induced liver disease autoimmune liver disease primary biliary cholangitis primary sclerosing cholangitis others comorbidities chronic obstructive pulmonary disease diabetes mellitus hypertension coronary artery disease renal failure obesity immunosuppressive drugs
Primary endpoint Seroconversion or immunity is defined as HBsAb level 10 mIUml
Randomization process
Investigators will use the envelope allocation technique At first Investigators will create a sequentially numbered random group assignment The supplies for the randomization envelopes include envelopes back carbon paper and white copy paper On the white copy paper Investigators will write the study ID Investigators will wrap the white copy paper inside the black carbon paper put those into the envelope and seal it
The above data will be prospectively collected and entered into an excel database in a de-identified mode by giving them a coded number Investigators will save data in a password-protected format and filed in the GI Research share drive and only the study staff will have access to the file to download for any study procedure or audit It will be stored in a confidential manner indefinitely in a secured Mercy share drive according to the 21 CFR part 11 guidelines
The sample size for both arms total 200 The current seroconversion rate of the hepatitis B vaccine in cirrhosis is low about 50 with the conventional schedule either Engerix 0 1 month 6 months or Heplisav-B 0 1 month Investigators aim for the seroconversion rate of 70 with Heplisav-B 0 1 month 2 months The probability of type I error is 5 and the power is 80
Hepatitis B virus is a major cause of acute and chronic liver disease both in the United States and worldwide In 2016 an estimated 862000 people were living with HBV infection in the US with a total of 1649 US death certificates recorded as an underlying or contributing cause of death Chronic infection may cause liver cirrhosis and hepatocellular carcinoma HCC Since the introduction of the vaccine in the 1990s there has been a significant decline in the incidence of HBV infection Approved in November 2017 Heplisav-B uses a synthetic cytosine phosphoguanine oligonucleotide derived from bacterial DNA it is thought to stimulate the immune system through activation of the toll-like receptor 9 pathway which induces the production of cytokines such as interleukines such as interleukine-12 and interferon-alpha It has been shown to induce higher immunity in healthy individuals compared to conventional vaccines
The HBsAb titer should be checked 8 to 12 weeks after the administration of the vaccination series Good responders were defined as those having the anti-HBs titer were 100 mUIml poor responders having anti-HBs titer between 10 and 99 mUIml and nonresponders having anti-HBs titer 10 mIUml The Seroprotection rate by age group in the healthy population is 100 in the 18-29-year-old group 989 in the 30-29 -year-old group 972 in the 40-49-year-old group 952 in the 50-59-year-old group 916 in 60-70-year-old group However 5 of the general population will not mount a protection response
Response to HBV vaccine is variable among patients with chronic diseases such as HIV infection celiac disease IBD end-stage renal disease diabetes The immunogenicity of the hepatitis B vaccine is also lower in decompensated cirrhosis Among cirrhotic patients only 45 who received Heplisav-B achieved immunity in investigators previous retrospective analysis The usual approach to HBV vaccine nonresponse is repeating the vaccine series in noninfected individuals
Investigational Plan
Study Design Duration Patients with cirrhosis or chronic liver disease presented to the hepatology clinic in Mercy Medical Center between 092020 and 072021 who do not have immunity against Hepatitis B defined as anti-HBs titer 10 mIUml will be recruited Patients will be stratified based on cirrhosis vs no-cirrhosis and vaccine naive vs vaccine experienced Patients who had more than one vaccination series will not be included Previous vaccination could be either Heplisav or Engerix however this information will be collected The investigators plan is to do the 1st part of the study is in treatment-naive patients and expand it to vaccine experienced
Investigators will randomize patients to receive Heplisav-B in 0 4 weeks or Heplisav-B in 0 4 8 weeks The HBV surface antibody titer will be checked 8 to 12 weeks after administration of the vaccination series and classified into good responders poor responders and nonresponders based on antibody titers
Investigators will collect basic data including age MELD scores etiologies of cirrhosis non-alcoholic fatty liver disease hepatitis C alcohol-induced liver disease autoimmune liver disease primary biliary cholangitis primary sclerosing cholangitis others comorbidities chronic obstructive pulmonary disease diabetes mellitus hypertension coronary artery disease renal failure obesity immunosuppressive drugs
Primary endpoint Seroconversion or immunity is defined as HBsAb level 10 mIUml
Randomization process
Investigators will use the envelope allocation technique At first Investigators will create a sequentially numbered random group assignment The supplies for the randomization envelopes include envelopes back carbon paper and white copy paper On the white copy paper Investigators will write the study ID Investigators will wrap the white copy paper inside the black carbon paper put those into the envelope and seal it
The above data will be prospectively collected and entered into an excel database in a de-identified mode by giving them a coded number Investigators will save data in a password-protected format and filed in the GI Research share drive and only the study staff will have access to the file to download for any study procedure or audit It will be stored in a confidential manner indefinitely in a secured Mercy share drive according to the 21 CFR part 11 guidelines
The sample size for both arms total 200 The current seroconversion rate of the hepatitis B vaccine in cirrhosis is low about 50 with the conventional schedule either Engerix 0 1 month 6 months or Heplisav-B 0 1 month Investigators aim for the seroconversion rate of 70 with Heplisav-B 0 1 month 2 months The probability of type I error is 5 and the power is 80
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None