IMPAACT 1077HS: HAART Standard Version of the Promoting Maternal and Infant Survival Everywhere (PROMISE) Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,653
- 试验地点
- 50
- 主要终点
- Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death
研究概览
简要总结
This study was a randomized strategy trial conducted among women who received highly active antiretroviral therapy (HAART) during pregnancy for purposes of prevention of mother-to-child transmission (PMTCT) of HIV but did not otherwise meet criteria to initiate HAART for their own health. The study was designed to determine whether continuation of HAART after delivery or other pregnancy outcome reduced morbidity and mortality compared to discontinuation and re-initiation of HAART when protocol specified criteria were met.
详细描述
This randomized strategy trial addressed therapeutic questions for women from regions where antepartum HAART for PMTCT (for all CD4+ cell counts) and postpartum formula feeding is standard of care, and who also had both a pre-HAART CD4+ cell count >400 cells/mm^3 and a screening (on-HAART) CD4+ cell count > 400 cells/mm^3. For these women, the objectives related to the relative efficacy and safety of continuing HAART (when it is no longer used for PMTCT) versus discontinuing HAART.
Potential participants were identified/recruited and consented during pregnancy or after delivery or other pregnancy outcome. Study-specific screening was initiated in the third trimester or after pregnancy outcome. Women who were screened for the study were counseled to continue their HAART until they were randomized.
Randomization would occur within 0-42 days after pregnancy outcome. Women who did not carry their pregnancy to the third trimester but otherwise meet study eligibility criteria could be enrolled.
Participants were randomized to one of the two study arms:
Arm A: Continuation of HAART Arm B: Discontinuation of HAART and resume HAART when protocol-specified criteria were met
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women age ≥ 18 years or who had attained the minimum age of independent consent, as defined by the local Institutional Review Board (IRB), and were willing and able to provide written informed consent Additionally, at sites with IRB approval to enroll younger participants, women age 16-17 years who were willing and able to provide written assent and whose parent or legal guardian was willing and able to provide written informed consent
- •Confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry, using protocol-specified tests (see protocol for more details)
- •Documentation of hepatitis B surface antibody (HBsAb) status and hepatitis B surface antigen (HBsAg) status (if antibody was negative) within 12 months prior to study entry
- •Within 0-42 days after pregnancy outcome
- •Antiretroviral treatment naïve, defined as < 14 days of one or more antiretroviral agents, prior to therapy initiated during current pregnancy
- •Receipt of at least four weeks of HAART prior to study entry, at least two weeks of which must have been prior to pregnancy outcome (up to seven consecutive days of missed therapy is permitted)
- •CD4+ cell count ≥ 400 cells/mm^3 on a specimen obtained within 120 days prior to initiation of HAART for current pregnancy
- •CD4+ cell count ≥ 400 cells/mm^3 on a specimen obtained on HAART and within 45 days prior to study entry
- •The following laboratory values on a specimen obtained within 45 days prior to study entry:
- •Absolute neutrophil count ≥ 750/mm^3
- •Hemoglobin ≥ 7.0 g/dL
- •Platelet count ≥ 50,000/mm^3
- •AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN
- •Estimated creatinine clearance of ≥ 60mL/min within 45 days prior to entry using the Cockcroft-Gault formula
- •Intent to remain in current geographical area of residence for the duration of the study
- •Willingness to attend study visits as required by the study
排除标准
- •Previous participation in PROMISE (P1077BF - NCT01061151)
- •Clinical indication for HAART including any World Health Organization (WHO) Clinical Stage 3 or 4 condition, prior or current tuberculosis disease (a positive (Purified protein Derivative) PPD test alone was not considered exclusionary), and/or any other clinical indication per country-specific treatment guidelines
- •Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
- •Social or other circumstances which, in the opinion of the site investigator, would hinder long-term follow up
- •Use of any prohibited medications within 14 days prior to study entry (refer to the study MOP for a list of prohibited medications)
- •Current compulsory detention (involuntary incarceration) in a correctional facility, prison, or jail for legal reasons or compulsory detention in a medical facility for treatment of either a psychiatric or physical (e.g., infectious disease) illness
- •Currently breastfeeding or planning to breastfeed
- •Current documented conduction heart defect (specialized assessments to rule out this condition were not required; a heart murmur alone and/or type 1 second-degree atrioventricular block (also known as Mobitz I or Wenckebach) was not considered exclusionary)
- •Known evidence of HBV DNA levels >2000 IU/mL (approximately 10,000 copies/mL) in the presence of elevated (grade 1 and higher) ALT (HBV DNA testing was not required for study screening or enrollment but was considered to determine whether treatment for HBV was indicated)
研究组 & 干预措施
Continue HAART
Continue receiving HAART within 0-42 days after delivery or other pregnancy outcome.
干预措施: Highly active antiretroviral therapy (HAART) (Drug)
Stop HAART
Stop receiving HAART within 0-42 days after delivery or other pregnancy outcome and resume HAART when protocol specified criteria were met.
干预措施: Highly active antiretroviral therapy (HAART) (Drug)
结局指标
主要结局
Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death
时间窗: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
AIDS defining illness, serious non-AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.
次要结局
- Incidence Rate of AIDS - Defining Illness(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of Deaths(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of HIV/AIDS Related Events(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of HIV/AIDS Related Events or Death(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of Grade 2 and Above Toxicity(All laboratory measures were done at entry,4 and 12 weeks after, and then every 3 months until study end. Signs and Symptoms were recorded from study entry to study end. All were followed until July 7, 2015 (an average of 125 weeks of follow-up))
- Incidence Rate of Cardiovascular or Other Metabolic Events(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of Other Targeted Medical Conditions(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Incidence Rate of Any Condition Outlined in Appendix II of Protocol or Death(From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm(At time of confirmation of VF. HIV-1 RNA testing to identify VF was done at week 4, 12, 24, and every 12 weeks thereafter until study end at an average of 125 weeks. If HIV-1 RNA was above 1000 copies/ml, confirmatory testing was done within 4 weeks.)
- Medication Adherence - Last Time Missed Medications(week 0, 48 and 96)
- Medication Adherence - How Closely Followed Schedule(week 0, 48 and 96)
- Medication Adherence - How Often Follow Instructions(week 0, 48 and 96)
- Medication Adherence - Missed Dose Within Past 4 Days(week 0, 48 and 96)
- Quality of Life - General Health Outcome(week 0, 48 and 96)
- Quality of Life (QoL) - Health Rating Score(week 0, 48 and 96)
- Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers(Measured at baseline, after 4 and 12 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)
- Cost Effectiveness and Feasibility of Treatment Models(Measured at baseline, after 4 - 12 and 24 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).)