Simplifying Hepatitis B Care in Pregnancy by Combining Birth-dose Vaccine and Tenofovir: The COMBAT HBV Feasibility Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 317
- 试验地点
- 1
- 主要终点
- Safety (Pregnant Women): Number of Pregnant Women With Adverse Effects Related to Study Medications
研究概览
简要总结
This is a double-blind, randomized placebo-controlled trial (RCT) of a prophylaxis-for-all approach to prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in the Democratic Republic of Congo (DRC). HBV-infected pregnant women will be randomized to either receive tenofovir or placebo beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Women will be followed every 4-6 weeks throughout the prenatal and postpartum period to evaluate for side effects related to the medication. Infants will receive a birth-dose of HBV vaccine, ideally within 24 hours. Participants will be followed longitudinally through 6 months' postpartum.
详细描述
The overall study design is a randomized, double-blind, placebo-controlled trial among two groups of mother-infant dyads: women who receive TDF vs placebo in late pregnancy and the postpartum period (beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum). While official World Health Organization (WHO) recommendations are to continue TDF at least through delivery, a range from delivery through 12 weeks' postpartum is possible; the investigators will continue therapy through 4 weeks' postpartum in this study. This feasibility trial will evaluate the acceptability, safety and preliminary effectiveness of a TDF-for-all approach to prevent MTCT of HBV in low-resource settings. HBsAg-positive pregnant women will be enrolled at 28-32 weeks' gestation, and will present for regular medication checks, with a study closeout visit at 24 weeks' postpartum. Study activities at monthly medication checks will include medication refills, assessment of adherence (via pill counts and verbal surveys), and evaluation for side effects. All infants will receive a birth-dose of HBV vaccine within 24 hours of life. MTCT of HBV will be defined as the proportion of infants with positive HBsAg testing at 6 months. This pilot study will provide preliminary data for sample size calculations, including safety and effectiveness data, to prepare for larger RCTs to determine the effectiveness of a tenofovir-for-all approach, as well as the added benefit of tenofovir over birth-dose vaccination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The trial will be double-blinded, with study staff and participants blinded to allocation to the TDF vs placebo arm. Blinding to medication type will be achieved via use of over-encapsulation of TDF and placebo pills. Laboratory technicians who perform point-of-care hepatitis B core related antigen testing, HBV viral load testing and hepatitis B e antigen testing will be blinded to study arm.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pregnant women ≥18 years of age who present for routine prenatal care between 28-32 weeks' gestation and who test HBV-positive by point-of-care hepatitis B surface antigen test. Women must intend to seek maternity and postpartum care exclusively at one of the Kinshasa-based study maternity centers.
- •Infants born to enrolled women will be included in the study
排除标准
- •Individuals with abnormal creatinine by point-of-care testing
- •Any woman who plans to move outside of Kinshasa Province during the study period.
- •Any HIV-positive individual, determined by routine point-of-care screening at antenatal care visits
研究组 & 干预措施
Tenofovir disoproxil fumarate (TDF) arm
140 pregnant women in the experimental arm will receive tenofovir disoproxil fumarate (TDF) 300 milligrams (mg) daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.
干预措施: Tenofovir Disoproxil Fumarate 300 MG (Drug)
Tenofovir disoproxil fumarate (TDF) arm
140 pregnant women in the experimental arm will receive tenofovir disoproxil fumarate (TDF) 300 milligrams (mg) daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.
干预措施: Hepatitis B monovalent vaccine (Biological)
Placebo arm
140 pregnant women in the placebo arm will receive a placebo pill daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.
干预措施: Hepatitis B monovalent vaccine (Biological)
Placebo arm
140 pregnant women in the placebo arm will receive a placebo pill daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety (Pregnant Women): Number of Pregnant Women With Adverse Effects Related to Study Medications
时间窗: Up to study close-out visit, or up to 12 months
Safety of TDF prophylaxis in pregnant women, defined as a composite of adverse events (# mild adverse events \[AEs\], # moderate-to-severe AEs), presence of side effects and alanine aminotransferase elevations ≥ 5x upper limit of normal
Feasibility (Recruitment): Number of Eligible Participants Who Were Enrolled in the Study
时间窗: Up to study close-out visit, or up to 12 months
Recruitment is indicative of the number of pregnant women who are screened versus those actually enrolled in the study.
Acceptability (Lab Testing): Number of Mothers With Lab Testing Acceptability Scores >80%
时间窗: Upon study close-out visit, or up to 12 months
Number of mothers who report the process of undergoing lab draws as "acceptable" in the exit survey. Range 0-100%, with 0% being unacceptable and 100% being acceptable.
Feasibility (Maintenance): Proportion of Study Visits Completed Per Participant
时间窗: Up to study close-out visit (12 months)
Adherence to study visits and procedures, defined as proportion of the actual number of visits attended divided by the expected study visits (8) and multiplied by 100.
Acceptability (Medication): Number of Mothers With Medication Acceptability Scores >80%
时间窗: Upon study close-out visit, or up to 12 months
Number of mothers who report the process of taking the study medication as "acceptable" in the exit survey. Range 0-100%, with 0% being unacceptable and 100% being acceptable.
Feasibility (Retention): Number of Enrolled Participants Who Remain in the Study Through 6 Months Postpartum
时间窗: Up to study close-out visit, or up to 12 months
Retention is defined as the number of participants who remain in the study through the 6-month postpartum visit.
Feasibility (Refusal): Number of Eligible Participants Who Refused to Enroll in the Study
时间窗: Up to study close-out visit, or up to 12 months
Refusal will be defined as the number of individuals who refuse enrollment upon initial recruitment.
Feasibility (Withdrawal): Number of Enrolled Participants Who Withdraw from the Study
时间窗: Up to study close-out visit, or up to 12 months
Withdrawal is indicative of the number of enrolled participants who choose not to continue study activities after having been enrolled.
Preliminary Effectiveness: Number of Infants With HBV Positivity by Rapid Diagnostic Testing at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV
时间窗: Measured at 6 months after birth
Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life.
Safety (Infants): Number of Infants with Adverse Effects Related to Study Medications
时间窗: At delivery
Safety of maternal TDF for infants, defined as a composite of: Birth weight (grams), mid-upper arm circumference (centimeters), gestational age at delivery (weeks and days), delivery mode (vaginal vs C-section), APGAR scores (0-10), # of adverse events
次要结局
- Specificity of the Hepatitis B Core-Related Antigen Test(Measured at Enrollment)
- Sensitivity of the Hepatitis B Core-Related Antigen Test(Measured at Enrollment)