Carcinoma, Hepatocellular, Hepatitis B, Liver Cirrhosis
Conditions
Keywords
rapid test, screening, ELISA, hepatitis B virus, access to care
Brief summary
With over 280 000 chronic carriers, 2,500 new annual cases and 1,300 deaths each year, hepatitis B is currently a frequent and potentially severe disease in France, despite efforts towards prevention and effective care. In terms of prevention, France has very low immunization coverage (27.7%) and a high percentage of people ignoring HBV status (55%), leading to a delay in care. This is partly explained by poor knowledge of hepatitis B infection in the general population and an underestimation of the health impact of hepatitis B by doctors and health officials. Until recently, there have been no national guidelines governing its implementation (which is variable depending on the structures where screening is performed) and an insufficient evaluation of screening practices. Thus, data on the severity of liver disease, indications for treatment of HBV-infected patients and data on the use of vaccination for nonimmunized people are scarce. Furthermore, while HIV rapid tests are beginning to be used more widely, particularly to address the issue of people who do not come back and collect their results and to better adapt counselling, their usefulness to detect of hepatitis B virus has not been evaluated to date. The main objective of the Optiscreen B Study is to determine the benefit, if any, of using rapid tests as a screening tool to improve diagnosis, care and prevention of hepatitis B. Individuals risk of HBV-infection will be randomized into 2 groups, one group for which screening will be performed by usual serological test and a second group for which screening will be based on rapid tests. Centers will be selected to represent a diverse range of health centers whose aims include screening, prevention and/or vaccination.
Interventions
OTHERELISA testing
Enzyme-linked immuno-assay (ELISA) will be used to determine hepatitis B surface antigen (HBsAg) and anti-HBsAg antibody (anti-HBs Ab) status. Results will be given after test results are available (8-10 days).
OTHERRapid testing
A rapid test will be performed to determine the subjects' hepatitis B surface antigen (HBsAg, using VIKIA®) and anti-HBs antibody status (anti-HBs Ab, using Quick ProfileTM). Results will be given the same day.
Sponsors
ANRS, Emerging Infectious Diseases
Gilead Sciences
Roche Pharma AG
Mairie de Paris
BioMérieux
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Born in a country of middle or high HBV endemicity * Parents born in a country of middle or high HBV endemicity * Travellers or residents from a country of middle or high HBV endemicity * Blood, organ, tissue, sperm, and/or ovary donners or candidate donners. * Health-care workers suspected of coming into direct contact with an HBV-infected individual and/or exposed to blood or any biological products from an HBV-infected individual * Close contact with HBsAg-positive individuals (living in the same household, sexual partner, sharing needles, etc.) * Individuals with accidental exposure to HBV * Individuals with multiple sexual partners * Men who have sex with men * Pregnant women * Hemodialysis * Individuals requiring immunosuppressive therapy * Individuals with persistently elevated transaminase levels * HIV-positive * Intravenous drug users
Exclusion criteria
* Age \<18 years old * Not capable of providing informed consent * Already participated in a multi-center validation of HBV rapid tests * Having, in their possession, irrefutable results of a prior test for hepatitis B virus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Appropriately Seeking Care | 6 months | Subjects who are considered required to seek further care are as follows: * those who need HBV vaccination (non-immunized) * those who are infected with hepatitis B virus (infected) Of these patients, subjects who have achieved appropriate care are considered as follows: * non immunized subjects who have initiated HBV vaccination sequence (vaccinated) * infected subjects who seek health care at a specialized center, allowing to quantify the severity of liver-related disease (infected with care) The percentage of patients appropriately seeking care will be then calculated by the following formula: ((nb Vaccinated + nb infected with care) / (nb non-immunized + nb infected))\*100 |
Countries
France
Participant flow
Recruitment details
From 29 February 2012 to 5 July 2012, volunteers were recruited from five study centers in the Paris metropolitan region, which actively participate in HBV screening, vaccination, and care - two sexually transmitted disease clinics, one primary healthcare center, one general screening center, and one travel clinic.
Pre-assignment details
2061 participants were initially screened for eligibility. Of them, 625 did not meet inclusion criteria and 436 declined to participate. In total, 1000 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| ELISA Testing HBV infection status determined by enzyme-linked immuno-assay (ELISA)
ELISA testing: Enzyme-linked immuno-assay (ELISA) will be used to determine hepatitis B surface antigen (HBsAg) and anti-HBsAg antibody (anti-HBs Ab) status. Results will be given after test results are available (8-10 days). | 496 |
| Rapid Testing HBV infection status determined initially by a rapid test, then confirmed by enzyme-linked immuno-assay (ELISA).
ELISA testing: Enzyme-linked immuno-assay (ELISA) will be used to determine hepatitis B surface antigen (HBsAg) and anti-HBsAg antibody (anti-HBs Ab) status. Results will be given after test results are available (8-10 days).
Rapid testing: A rapid test will be performed to determine the subjects' hepatitis B surface antigen (HBsAg, using VIKIA®) and anti-HBs antibody status (anti-HBs Ab, using Quick ProfileTM). Results will be given the same day. | 499 |
| Total | 995 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incomplete intervention | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | ELISA Testing | Rapid Testing | Total |
|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 16 | 40.1 years STANDARD_DEVIATION 15.6 | 40.4 years STANDARD_DEVIATION 15.8 |
| HBV prevalence of birth country High (>8.0%) | 88 participants | 87 participants | 175 participants |
| HBV prevalence of birth country Intermediate (2.0-8.0%) | 116 participants | 137 participants | 253 participants |
| HBV prevalence of birth country Low (<2.0%) | 292 participants | 275 participants | 567 participants |
| Health insurance plan CMU | 31 participants | 27 participants | 58 participants |
| Health insurance plan Social security | 465 participants | 472 participants | 937 participants |
| Sex: Female, Male Female | 250 Participants | 272 Participants | 522 Participants |
| Sex: Female, Male Male | 246 Participants | 227 Participants | 473 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 496 | 0 / 499 |
| serious Total, serious adverse events | 0 / 496 | 0 / 499 |
Outcome results
Primary
Percentage of Patients Appropriately Seeking Care
Subjects who are considered required to seek further care are as follows: * those who need HBV vaccination (non-immunized) * those who are infected with hepatitis B virus (infected) Of these patients, subjects who have achieved appropriate care are considered as follows: * non immunized subjects who have initiated HBV vaccination sequence (vaccinated) * infected subjects who seek health care at a specialized center, allowing to quantify the severity of liver-related disease (infected with care) The percentage of patients appropriately seeking care will be then calculated by the following formula: ((nb Vaccinated + nb infected with care) / (nb non-immunized + nb infected))\*100
Time frame: 6 months
Population: Only participants needing further medical intervention were included in analysis: non-immunized (HBsAg negative, anti-HBc antibody negative, anti-HBs antibody negative) or infected (HBsAg positive).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELISA Testing | Percentage of Patients Appropriately Seeking Care | 5.7 percentage of participants |
| Rapid Testing | Percentage of Patients Appropriately Seeking Care | 4.0 percentage of participants |
Comparison: Power calculations were performed to detect \>15% difference in immediate linkage-to-care and vaccination. We hypothesized from discussions with an expert panel that \~30% of participants would have appropriate care with standard HBV serology. Assuming type 1 error=0.05 and power=80%, 152 participants per arm would be needed. As \~40% of the population would be nonimmunized or HBsAg-positive from previous data, a minimum 375 participants per arm would be required.p-value: 0.5Chi-squared