Clinical trial NCT06023056: Hepatitis B Vaccination After Neonatal Surgery
Official title: Influence of Delayed Vaccination of Hepatitis B Vaccine on Vaccination Safety and Immune Response of Newborns After Gastrointestinal Surgery
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Vaccination Reaction
Hepatitis B Virus Infection
Digestive System Disorders of Fetus and Newborn
Blood Transfusion Complication
Hepatitis B Vaccine Adverse Reaction
Keywords: Hepatitis B Vaccination Reaction
Hepatitis B Vaccine Adverse Reaction
Neonatal surgery
Gastrointestinal Surgery
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2023-09-05
Enrollment: 180
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Follow up the neonates who live in the medical institution and meet the inclusion criteria. The end point of the study is 6 years after enrollment. Two mid-term evaluations will be conducted one year and two years after the start of the study. This project applies for funding until the mid-term evaluation of the first year. The follow-up research funds will be supported by the follow-up projects or self raised funds. The criteria for withdrawal from the cohort were: during the study period, the children were infected with hepatitis B virus due to other reasons such as "surgery, blood transfusion, trauma", or diagnosed with immune related diseases during the follow-up period.

Brief summary: At present, whether the hepatitis B vaccine (HBV) can be vaccinated on time after neonatal surgery has become a common problem for children's families, neonatal surgeons, and vaccination departments, but there are few relevant studies at home and abroad, and there is no corresponding guide or consensus. In the early stage, our research team investigated the vaccination plans of the vaccination units in the main urban areas of Chongqing for such children through telephone follow-up, and found that the practices of each unit were different, all based on their own experience, and there was no clear evidence to support the vaccination or should not be vaccinated, which may cause some children to miss the best vaccination time or increase the risk of vaccination. The center is a relatively large neonatal surgery center in southwest China. The diagnosis and treatment of neonatal digestive tract malformations is at the leading level in China. It can carry out various neonatal operations such as neonatal necrotizing enterocolitis, congenital anorectal malformations, and congenital megacolon. On average, it carries out more than 30 third and fourth grade neonatal gastrointestinal operations every month. It has accumulated a lot of experience in the follow-up of newborns, There is a large amount of clinical data support for children who need to be vaccinated after surgery, so it is planned to follow up the second and third doses of hepatitis B vaccine and whether there are adverse reactions related to vaccination for children who need to be vaccinated after gastrointestinal surgery in the neonatal period, and at the same time check the production of HBsAb after vaccination, The immune response and adverse reactions of hepatitis B vaccine at different time points after surgery were studied to increase clinical evidence for the determination of hepatitis B vaccine vaccination program for newborns after surgery.

Detailed description: Research design

1. Selection of research objects (research population)

Newborns who were screened in the department and met all of the following criteria were included in this study: 1) term infants and the first dose of hepatitis B vaccine had been vaccinated on time; 2) Children with indications for staged gastrointestinal surgery, and the first operation should be performed within 28 days after birth; 3) The child has no immune system disease or serious development defect or dysfunction of heart, brain, liver, kidney and other organs; 4) HBsAg - before initial operation; 5) Prenatal HBsAg - detection of the mother or father of the child; 6) The guardian signed the informed consent form and agreed to participate in the study. Exclusion criteria: 1) premature infants; 2) The first operation time exceeds 28 days after birth; 3) There are serious developmental malformations or dysfunction of heart, brain, liver, kidney and other organs or immune system diseases; 4) The patient or one of his parents is HBsAg+; 5) Children who are allergic to hepatitis B vaccine or have other serious adverse reactions; 6) Children interviewed by vector.

The end point of the study is 6 years after joining the group. Two mid-term evaluations will be conducted one year and two years after the start of the study. This project will apply for funding until the mid-term evaluation of the first year. The follow-up research funds will be supported by the follow-up projects or self raised funds. The criteria for withdrawal from the cohort were: during the study period, the children were infected with hepatitis B virus due to other reasons such as "surgery, blood transfusion, trauma", or diagnosed with immune related diseases during the follow-up period.

2. Patient grouping

1. Newborns who need to undergo gastrointestinal staging surgery as the research object can be included in this study after meeting the inclusion criteria and obtaining the consent of the guardian;
2. The children included in this study were divided into "delayed vaccination group after surgery" and "standard vaccination group after surgery" according to the evaluation of the community vaccination department. At the same time, 1-year-old and 2-year-old children with indirect inguinal hernia who were vaccinated according to the standard immunization program and had no other diseases were taken as the "control group";
3. Collect the general information of the "delayed vaccination group after operation" and the "standard vaccination group after operation", the mother's prenatal hepatitis B two-and-a-half, the children's hepatitis B vaccination time, the adverse reactions of hepatitis B vaccination, and the children's hepatitis B two-and-a-half before each hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface antibody in delayed vaccination group, standard vaccination group and control group was compared;
4. Collect the remaining serum of "Postoperative Delayed Inoculation Group" and "Postoperative Standard Inoculation Group" for HBV DNA detection;
5. The definition of bias refers to ROBINS-I standard, including bias caused by confusion, bias in the selection of research objects, bias in the classification of intervention measures, bias deviating from the expected intervention measures, bias caused by missing data in the outcome measurement and bias in selective reporting of results. Bias is divided into four levels: mild, moderate, severe and extremely severe.

3. Interventions

All the operated children were treated in Liangjiang Neonatal Surgery Department of Children's Hospital Affiliated to Chongqing Medical University. Before operation, they were examined for hepatitis B and HBV DNA.

4. Follow up plan

Collect the general information of the "delayed vaccination group after operation" and the "standard vaccination group after operation", the mother's prenatal hepatitis B two-and-a-half, the children's hepatitis B vaccination time, the adverse reactions of hepatitis B vaccination, and the children's hepatitis B two-and-a-half before each hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface antibody in delayed vaccination group, standard vaccination group and control group was compared; Collect the remaining serum of "Postoperative Delayed Inoculation Group" and "Postoperative Standard Inoculation Group" for HBV DNA detection;

5. Main measurement indexes

Collect the general information of the enrolled children, the mother's two pairs and a half of hepatitis B before delivery, the children's hepatitis B vaccination time, the adverse reactions of hepatitis B vaccination, and the children's two pairs and a half of hepatitis B before each hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface antibody in the delayed vaccination group, the standard vaccination group and the control group were compared.

6. Sample size calculation

According to the previous statistics, the average value of HBsAb of 992 neonates in our outpatient department was 349.5 IU/L, the standard deviation was 420.59 IU/L, and the average value of HBsAb of 1317 1-year-old children was 575.5 IU/L. Therefore, it is estimated that HBsAb will increase by 226 IU/L during the 1-year follow-up α= 0.05， β= 0.1, calculated according to the following formula.

Data management

1. Data entry

   This project uses EpiData to establish the database. The database designer determines the database creation requirements and database structure according to the case report form (CRF form) to ensure that the database content and structure are consistent with the CRF form, and the specified data can be properly entered into the database. The xx database is strictly password protected, and only the personnel directly involved in the research can obtain the password/account. According to the original observation records of the subjects, the researchers timely, completely, correctly and clearly loaded the data into the CRF table. The CRF form reviewed and signed by the investigator shall be submitted to the clinical research data administrator in time. The research data are entered into the EpiData database by authorized researchers. The database system of EpiData is used for double person and double computer input, and then the database is compared twice. Data changes due to input errors or other reasons will be recorded in detail and confirmed by the researcher. The questions and answers between the data administrator and the researcher are in the form of question table, which is kept for future reference.
2. Contents and methods of data verification and management

   Key points and process of data verification, as well as requirements for data locking. For example, when all case report forms have been entered in duplicate and checked without error, data cleaning has been completed, all queries have been answered or explained, and data quality control has been completed, the data administrator will write a database inspection report, which includes the completion of the study (including the list of dropped subjects), inclusion/exclusion criteria, integrity check, logic consistency check, outlier data check, time window check, drug combination check Adverse event inspection, etc. The researcher confirmed that the database will be locked.
3. Safety evaluation

   All adverse events were recorded. In particular, incidents that resulted in hospitalization, prolonged hospitalization, additional surgical or medical treatment, or death were reported.
4. Quality control and quality management

Before the start of the study, patients were enrolled in strict accordance with the inclusion and exclusion criteria, standardized case report forms (CRF) were developed, and ethical review and clinical study registration were confirmed; During the research, ensure the integrity of CRF table data records, the consistency of original data and CRF data, the security of data archiving, review the completion progress and queue interruption, and analyze the preciseness of data; After the study, confirm the integrity of statistical data, the standardization of statistical methods, the standardization of paper writing, and update the clinical study registration data.

Eligibility criteria: Inclusion Criteria:

1. Term neonates; 2. Underwent staged gastrointestinal surgery; 3. HBsAg-; 4. No immune system disease; 5.no serious defect of heart, brain, liver, kidney and other organs.

Exclusion Criteria:

1. Premature; 2. HBsAg+; 3. Having immune system diseases; 4. Having serious defect of heart, brain, liver, kidney and other organs; 5. Lost patients.

Primary outcomes:
measure: Prenatal hepatitis B surface markers
timeFrame: 1 month
measure: Newborn condition
timeFrame: 1 month
measure: Vaccination time
timeFrame: up to 2 years
measure: Adverse reactions
timeFrame: 2 years
measure: Immune effect of vaccine
timeFrame: up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Hanbin Zhao, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(2):1-64.
citation: Szilagyi PG, Rodewald LE. Missed opportunities for immunizations: a review of the evidence. J Public Health Manag Pract. 1996 Winter;2(1):18-25. doi: 10.1097/00124784-199600210-00005.