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IMPAACT 1077HS: Examining Benefits of HAART Continuation in Postpartum Women

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ClinicalTrials.gov Identifier: NCT00955968
Recruitment Status : Completed
First Posted : August 10, 2009
Results First Posted : February 19, 2018
Last Update Posted : August 10, 2020
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Tracking Information
First Submitted Date  ICMJE August 7, 2009
First Posted Date  ICMJE August 10, 2009
Results First Submitted Date  ICMJE August 30, 2017
Results First Posted Date  ICMJE February 19, 2018
Last Update Posted Date August 10, 2020
Actual Study Start Date  ICMJE January 2010
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2018)
Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2009)
Morbidity and mortality [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2020)
  • Incidence Rate of AIDS - Defining Illness [ Time Frame: 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, 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.
  • Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    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.
  • Incidence Rate of Deaths [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    The incidence rate was obtained by using the Kaplan-Meier method.
  • Incidence Rate of HIV/AIDS Related Events [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    HIV/AIDS related events 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.
  • Incidence Rate of HIV/AIDS Related Events or Death [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    HIV/AIDS related events 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.
  • Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    HIV/AIDS related events or WHO Clinical Stage 2 or 3 events 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.
  • Incidence Rate of Grade 2 and Above Toxicity [ Time Frame: 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) ]
    The toxicity events included all grade 2 and higher hematology or chemistry events and grade 3 or 4 sign or symptoms. These events were graded using the Division of AIDS (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com). The incidence rate was obtained by using the Kaplan-Meier method.
  • Incidence Rate of Cardiovascular or Other Metabolic Events [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
  • Incidence Rate of Other Targeted Medical Conditions [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
  • Incidence Rate of Any Condition Outlined in Appendix II of Protocol or Death [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
  • Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm [ Time Frame: 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. ]
    VF was defined as two successive measurements of HIV-1 RNA above 1000 copies/ml at or after 24 weeks of HAART. HIV drug resistance was defined using the Stanford database (Version 6.2)
  • Medication Adherence - Last Time Missed Medications [ Time Frame: week 0, 48 and 96 ]
    Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
  • Medication Adherence - How Closely Followed Schedule [ Time Frame: week 0, 48 and 96 ]
    Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
  • Medication Adherence - How Often Follow Instructions [ Time Frame: week 0, 48 and 96 ]
    Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
  • Medication Adherence - Missed Dose Within Past 4 Days [ Time Frame: week 0, 48 and 96 ]
    Medication adherence was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
  • Quality of Life - General Health Outcome [ Time Frame: week 0, 48 and 96 ]
    Quality of Life was evaluated by a self reported questionnaire. The number of participants who indicated predefined choice is provided.
  • Quality of Life (QoL) - Health Rating Score [ Time Frame: week 0, 48 and 96 ]
    QoL - health rating score was evaluated by a self reported questionnaire. Health rating score of 0 was indicative of death or worst possible health and a score of 100 was being in perfect or best possible health and the mean of score is calculated. Higher scores indicate better Quality of Life (QoL). The range is 0-100 units on a scale
  • Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers [ Time Frame: 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). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. This outcome required additional funding for laboratory testing which was not available and so this outcome is not reported.
  • Cost Effectiveness and Feasibility of Treatment Models [ Time Frame: 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). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses. Given the results of the primary analyses and changes in WHO guidelines to recommend lifelong antiretroviral therapy, the protocol team decided that this outcome was no longer scientifically important. No resources and funding was allocated by NIH.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2009)
  • Toxicity and side effects of medications [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
  • Emergence of HIV resistance [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
  • Medication Adherence [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
  • Quality of life [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
  • Cost Effectiveness and Feasibility of Treatment Models [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
  • Symptoms and lab values associated with clinical events [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
  • Incidence of AIDS-defining illnesses and other select medical conditions [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 3 months until study termination ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IMPAACT 1077HS: Examining Benefits of HAART Continuation in Postpartum Women
Official Title  ICMJE IMPAACT 1077HS: HAART Standard Version of the Promoting Maternal and Infant Survival Everywhere (PROMISE) Study
Brief Summary 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.
Detailed Description

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

Participants were to be followed until 84 weeks after the last participant was randomized.

Key evaluations were conducted at Screening, Entry, post entry visits were scheduled to take place 4 weeks after entry, 12 weeks after entry, and every 12 weeks thereafter. Key evaluations included physical examinations, clinical assessments, and blood collection.

On 7 July 2015, the study sites received formal communications regarding the results of the Strategic Timing of Antiretroviral Treatment (START) study and associated changes were implemented to the 1077HS study in response to these results. All sites were instructed that all women in the 1077HS study were to be informed of the START study results and that antiretroviral therapy (ART) was recommended for all women based on the START study results.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infection
Intervention  ICMJE Drug: Highly active antiretroviral therapy (HAART)

A combination of three or more HIV medications belonging to two or more drug classes.

The preferred study-supplied HAART regimen was lopinavir/ritonavir (LPV/RTV) plus fixed dose combination tenofovir/emtricitabine (TDF/FTC). Additional ARVs provided for use in this study included fixed dose combination lamivudine/zidovudine (3TC/ZDV), lamivudine (3TC), zidovudine (ZDV), tenofovir (TDF), fixed dose combination tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV), didanosine (ddI), atazanavir (ATV), raltegravir (RAL), and ritonavir (RTV). While LPV/RTV plus TDF/FTC was the preferred study-supplied regimen, the study clinicians in conjunction with participants would determine the optimal drug combination for each participant.

Study Arms  ICMJE
  • Experimental: Continue HAART
    Continue receiving HAART within 0-42 days after delivery or other pregnancy outcome.
    Intervention: Drug: Highly active antiretroviral therapy (HAART)
  • Active Comparator: Stop HAART
    Stop receiving HAART within 0-42 days after delivery or other pregnancy outcome and resume HAART when protocol specified criteria were met.
    Intervention: Drug: Highly active antiretroviral therapy (HAART)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2015)
1653
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2009)
2000
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Botswana,   Brazil,   China,   Haiti,   Peru,   Puerto Rico,   Thailand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00955968
Other Study ID Numbers  ICMJE IMPAACT 1077HS
U01AI068632 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Study Sponsor  ICMJE International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Collaborators  ICMJE
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Study Chair: Judith S. Currier, MD, MS University of California, Los Angeles
PRS Account International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP