HIV-1-infection, Pre-term Birth
Conditions
Keywords
PreTerm Birth, HIV-1-infection, Antiretroviral Treatment
Brief summary
This is a phase III, double-masked, placebo-controlled, randomized controlled trial taking place in Zambia.
Detailed description
Weekly intramuscular injections of 250mg 17-alpha hydroxyprogesterone caproate (17P) or indistinguishable placebo will be randomly allocated in a 1:1 ratio started between 16-24 weeks gestation and administered weekly thereafter until 36 6/7 gestational weeks, stillbirth, or delivery, whichever is sooner. Individual participants will be followed from enrollment (prior to 24 weeks gestation) through 42 days postpartum.
Interventions
DRUG17P
Synthetic progestin
OTHERPlacebo
Non-active placebo comparator
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
AMAG Pharmaceuticals, Inc.
Bill and Melinda Gates Foundation
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Phase III, double-masked, placebo-controlled, randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * less than 24 0/7 weeks of gestation * viable intrauterine singleton pregnancy confirmed by ultrasound * antibody-confirmed HIV-1 infection * currently receiving antiretroviral l therapy (ART) or intending to commence ART in pregnancy * ability and willingness to provide written informed consent * intent to remain in current geographical area of residence for the duration of study * willing to adhere to weekly study visit schedule
Exclusion criteria
* confirmed prior spontaneous preterm birth * multiple gestation * known uterine anomaly * planned or in situ cervical cerclage * major fetal anomaly detected on screening ultrasound * indication for planned delivery prior to 37 weeks (e.g., prior classical cesarean) * threatened abortion, preterm labor, or ruptured membranes at time of enrollment * known allergy or medical comorbidity listed as a contraindication to 17P in the prescribing information * prior participation in the trial * any other condition (social or medical) which, in the opinion of the study staff, would make trial participation unsafe or complicate data interpretation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Preterm Births or Stillbirths | At delivery, up to 37 weeks of gestation for live births and up to approximately 40 weeks of gestation for stillbirths | A composite of live births prior to 37 weeks of gestation or stillbirth occurring at any gestational age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Preterm Birth <34 Weeks | At delivery, up to 34 weeks of gestation | Delivery prior to 34 gestational weeks |
| Number of Participants Experiencing Preterm Birth <28 Weeks | At delivery, up to 28 weeks of gestation | Delivery prior to 28 gestational weeks |
| Number of Participants Experiencing Stillbirth | At delivery, up to approximately 40 weeks of gestation | Participants who had a fetus born without signs of life at any gestational age |
| Number of Participants Experiencing Spontaneous Delivery <37 Weeks | At delivery, up to 37 weeks of gestation | Delivery prior to 37 weeks of gestation that was initiated spontaneously, without provider intervention |
| Number of Participants Experiencing Spontaneous Delivery <34 Weeks | At delivery, up to 34 weeks of gestation | Delivery prior to 34 weeks of gestation that was initiated spontaneously, without provider intervention |
| Number of Participants Experiencing Spontaneous Delivery <28 Weeks | At delivery, up to 28 weeks of gestation | Delivery prior to 28 weeks of gestation that was initiated spontaneously, without provider intervention |
| Number of Participants Experiencing Preterm Birth <37 Weeks | At delivery, up to 37 weeks of gestation | Delivery prior to 37 gestational weeks |
| Number of Infants With Birth Weight <3rd Percentile for Gestational Age | Birth | Infant born with a weight below the 3rd percentile for gestational age |
| Number of Infants Who Experienced Maternal-to-Child HIV Transmission | At 6 weeks of life | Confirmed HIV infection in an infant |
| Number of Neonatal Deaths | Birth through 28 days postpartum | Death of an infant following live birth |
| Number of Infants With 1-minute Apgar Score <7 | 1 minute of life | Apgar score of less than 7 at 1 minute of life. Apgar stands for Appearance, Pulse, Grimace, Activity, and Respiration and is a quick test rated on a scale of 1-10 performed on a baby at one minute of life to determine how well the baby tolerated the birth process. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low. |
| Number of Infants With 5-minute Apgar Score <7 | 5 minutes of life | Apgar score of less than 7 at 5 minutes of life. Apgar stands for Appearance, Pulse, Grimace, Activity, and Respiration and is a quick test rated on a scale of 1-10 performed on a baby at five minutes of life to assess how well the baby is doing following delivery. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low. |
| Number of Infants With Birth Weight <10th Percentile for Gestational Age | Birth | Infant born with a weight below the 10th percentile for gestational age |
Countries
Zambia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mothers: 250 mg 17P Mothers started study intervention between 16-24 weeks gestation and were administered weekly injections thereafter until 36 6/7 gestational weeks, stillbirth, or delivery, whichever is sooner. Participants followed from enrollment (prior to 24 weeks gestation) through 42 days postpartum.
17P: Synthetic progestin | 399 |
| Mothers: Placebo Mothers started study intervention between 16-24 weeks gestation and were administered weekly injections thereafter until 36 6/7 gestational weeks, stillbirth, or delivery, whichever is sooner. Participants followed from enrollment (prior to 24 weeks gestation) through 42 days postpartum.
Placebo: Non-active placebo comparator | 401 |
| Total | 800 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Miscarriage | 0 | 2 |
Baseline characteristics
| Characteristic | Mothers: 250 mg 17P | Mothers: Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 399 Participants | 401 Participants | 800 Participants |
| Age, Continuous | 29 years | 30 years | 29 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 399 Participants | 401 Participants | 800 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 399 Participants | 401 Participants | 800 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Zambia | 399 Participants | 401 Participants | 800 Participants |
| Sex: Female, Male Female | 399 Participants | 401 Participants | 800 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 399 | 1 / 401 | 14 / 399 | 7 / 401 |
| other Total, other adverse events | 43 / 399 | 27 / 401 | 0 / 399 | 0 / 401 |
| serious Total, serious adverse events | 56 / 399 | 55 / 401 | 33 / 399 | 22 / 401 |
Outcome results
Primary
Number of Participants Experiencing Preterm Births or Stillbirths
A composite of live births prior to 37 weeks of gestation or stillbirth occurring at any gestational age
Time frame: At delivery, up to 37 weeks of gestation for live births and up to approximately 40 weeks of gestation for stillbirths
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Preterm Births or Stillbirths | 36 Participants |
| Placebo | Number of Participants Experiencing Preterm Births or Stillbirths | 36 Participants |
Secondary
Number of Infants Who Experienced Maternal-to-Child HIV Transmission
Confirmed HIV infection in an infant
Time frame: At 6 weeks of life
Population: Infants receiving a test for early infant diagnosis at approximately 6 weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Infants Who Experienced Maternal-to-Child HIV Transmission | 1 Participants |
| Placebo | Number of Infants Who Experienced Maternal-to-Child HIV Transmission | 1 Participants |
Secondary
Number of Infants With 1-minute Apgar Score <7
Apgar score of less than 7 at 1 minute of life. Apgar stands for Appearance, Pulse, Grimace, Activity, and Respiration and is a quick test rated on a scale of 1-10 performed on a baby at one minute of life to determine how well the baby tolerated the birth process. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.
Time frame: 1 minute of life
Population: Live born infants for whom an Apgar score was measured at 1 minute of life
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Infants With 1-minute Apgar Score <7 | 12 Participants |
| Placebo | Number of Infants With 1-minute Apgar Score <7 | 9 Participants |
Secondary
Number of Infants With 5-minute Apgar Score <7
Apgar score of less than 7 at 5 minutes of life. Apgar stands for Appearance, Pulse, Grimace, Activity, and Respiration and is a quick test rated on a scale of 1-10 performed on a baby at five minutes of life to assess how well the baby is doing following delivery. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.
Time frame: 5 minutes of life
Population: Live born infants for whom an Apgar score was measured at 5 minutes of life
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Infants With 5-minute Apgar Score <7 | 7 Participants |
| Placebo | Number of Infants With 5-minute Apgar Score <7 | 2 Participants |
Secondary
Number of Infants With Birth Weight <10th Percentile for Gestational Age
Infant born with a weight below the 10th percentile for gestational age
Time frame: Birth
Population: Liveborn or stillborn infants weighed at birth
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Infants With Birth Weight <10th Percentile for Gestational Age | 95 Participants |
| Placebo | Number of Infants With Birth Weight <10th Percentile for Gestational Age | 93 Participants |
Secondary
Number of Infants With Birth Weight <3rd Percentile for Gestational Age
Infant born with a weight below the 3rd percentile for gestational age
Time frame: Birth
Population: Live born or stillborn infants weighed at birth
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Infants With Birth Weight <3rd Percentile for Gestational Age | 28 Participants |
| Placebo | Number of Infants With Birth Weight <3rd Percentile for Gestational Age | 47 Participants |
Secondary
Number of Neonatal Deaths
Death of an infant following live birth
Time frame: Birth through 28 days postpartum
Population: Live born infants for whom follow-up information is available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Neonatal Deaths | 14 Participants |
| Placebo | Number of Neonatal Deaths | 7 Participants |
Secondary
Number of Participants Experiencing Preterm Birth <28 Weeks
Delivery prior to 28 gestational weeks
Time frame: At delivery, up to 28 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Preterm Birth <28 Weeks | 3 Participants |
| Placebo | Number of Participants Experiencing Preterm Birth <28 Weeks | 5 Participants |
Secondary
Number of Participants Experiencing Preterm Birth <34 Weeks
Delivery prior to 34 gestational weeks
Time frame: At delivery, up to 34 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Preterm Birth <34 Weeks | 14 Participants |
| Placebo | Number of Participants Experiencing Preterm Birth <34 Weeks | 16 Participants |
Secondary
Number of Participants Experiencing Preterm Birth <37 Weeks
Delivery prior to 37 gestational weeks
Time frame: At delivery, up to 37 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Preterm Birth <37 Weeks | 31 Participants |
| Placebo | Number of Participants Experiencing Preterm Birth <37 Weeks | 35 Participants |
Secondary
Number of Participants Experiencing Spontaneous Delivery <28 Weeks
Delivery prior to 28 weeks of gestation that was initiated spontaneously, without provider intervention
Time frame: At delivery, up to 28 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Spontaneous Delivery <28 Weeks | 3 Participants |
| Placebo | Number of Participants Experiencing Spontaneous Delivery <28 Weeks | 4 Participants |
Secondary
Number of Participants Experiencing Spontaneous Delivery <34 Weeks
Delivery prior to 34 weeks of gestation that was initiated spontaneously, without provider intervention
Time frame: At delivery, up to 34 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Spontaneous Delivery <34 Weeks | 10 Participants |
| Placebo | Number of Participants Experiencing Spontaneous Delivery <34 Weeks | 11 Participants |
Secondary
Number of Participants Experiencing Spontaneous Delivery <37 Weeks
Delivery prior to 37 weeks of gestation that was initiated spontaneously, without provider intervention
Time frame: At delivery, up to 37 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Spontaneous Delivery <37 Weeks | 25 Participants |
| Placebo | Number of Participants Experiencing Spontaneous Delivery <37 Weeks | 26 Participants |
Secondary
Number of Participants Experiencing Stillbirth
Participants who had a fetus born without signs of life at any gestational age
Time frame: At delivery, up to approximately 40 weeks of gestation
Population: Participants who received at least one injection of study product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 250 mg 17P | Number of Participants Experiencing Stillbirth | 10 Participants |
| Placebo | Number of Participants Experiencing Stillbirth | 11 Participants |