Pregnancy Complications
Conditions
Brief summary
Preterm birth is the leading cause of neonatal death and a significant cause of life long disability and health problems. It has been shown that the drug 17-hydroxyprogesterone caproate can help reduce the risk of preterm delivery in women with certain risk factors for preterm birth. We hope to learn whether this same medication can be used to prolong pregnancy in a group of patients in whom this medication has not been previously studied. Specifically, we hope to learn whether progesterone supplementation will delay delivery in women with pre-term, premature rupture of membranes (PPROM).
Detailed description
When women present to either the Obstetrical clinic or labor and delivery with a complaint of possible preterm, premature rupture of membranes (PPROM), they will be examined by an obstetrician to either confirm or rule out this diagnosis. If they are diagnosed with PPROM, they will then be admitted to Lucile Packard Children's Hospital and treated with the normal protocol which includes receiving antibiotics, receiving steroids, being hospitalized until delivery, and having ongoing maternal and fetal monitoring for possible complications. The patients will be identified by their treating obstetricians as possible study candidates and asked by a member of the treatment team if they are potentially interested in participating in a research study. Subsequently, a member of the study team or the treating physician will approach the patient about participating in the trial. Those who choose to participate will receive the standard care protocol in addition to receiving the study medication. The study medication will be a weekly injection of either placebo or 17-hydroxyprogesterone caproate or placebo. The placebo medication (castor oil) was chosen as it has been used in previous studies as a placebo for 17-hydroxyprogesterone caproate. The choice of which medication the patient receives will be determined by a randomization table. Only the pharmacist will be aware of the medication that has been administered. The patient, members of the treatment team, and members of the study team will be blinded to the medication that is being administered. The timing of their delivery will be managed by the treating obstetrician according to standard medical practice. After delivery, the patient's and her infant's medical outcomes will be recorded for analysis.
Interventions
Weekly injections of 17-hydroxyprogesterone caproate.
OTHERCaster Oil injections
Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
1. 18yr of age 2. Singleton pregnancy 3. PPROM confirmed on clinical exam 4. GA between 24+0 and 33+5 wk 5. Ability to understand consent in either English or Spanish
Exclusion criteria
1. Contraindication to ongoing pregnancy including: 1. Evidence of active infection 2. Evidence of significant placental abruption 3. IUFD diagnosed at the time of P-PROM diagnosis 2. Major fetal malformation 3. Maternal allergy to progesterone or placebo drug components 4. Current use of progesterone at the time of P-PROM 5. Multiple Gestations 6. Inability to understand consent in either English or Spanish
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Achievement of 34 Weeks Gestation | From enrollment until delivery, an average of 34 weeks | Delayed delivery until 34 weeks gestation. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Neonatal Respiratory Distress Syndrome | From delivery until neonatal hospital discharge, assessed up to 2 months |
| Number of Participants With Neonatal Grade III - IV Intraventricular Hemorrhage | From delivery until neonatal hospital discharge, assessed up to 2 months |
| Number of Participants With Neonatal Necrotizing Enterocolitis | From delivery to neonatal discharge, assessed up to 2 months |
| Neonatal Length of NICU and Total Hospital Stay Assessed as Number of Days | From birth to discharge form delivery hospital, assessed up to 2 months |
| Length of Latency Assessed as Number of Days | From rupture of membranes until delivery, assessed up to 34 weeks of gestation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 17-hydroxyprogesterone Caproate Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation
17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate. | 10 |
| Castor Oil Injections Weekly injections of Caster Oil (placebo)
Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation. | 11 |
| Total | 21 |
Baseline characteristics
| Characteristic | Castor Oil Injections | 17-hydroxyprogesterone Caproate | Total |
|---|---|---|---|
| Age, Continuous | 31.7 years STANDARD_DEVIATION 2 | 31.7 years STANDARD_DEVIATION 1.9 | 31.7 years STANDARD_DEVIATION 1.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 7 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| History of prior preterm birth | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 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 | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 0 / 10 | 0 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Number of Participants With Achievement of 34 Weeks Gestation
Delayed delivery until 34 weeks gestation.
Time frame: From enrollment until delivery, an average of 34 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 17-hydroxyprogesterone Caproate | Number of Participants With Achievement of 34 Weeks Gestation | 0 Participants |
| Castor Oil Injections | Number of Participants With Achievement of 34 Weeks Gestation | 0 Participants |
Secondary
Length of Latency Assessed as Number of Days
Time frame: From rupture of membranes until delivery, assessed up to 34 weeks of gestation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 17-hydroxyprogesterone Caproate | Length of Latency Assessed as Number of Days | 14.5 days |
| Castor Oil Injections | Length of Latency Assessed as Number of Days | 8 days |
p-value: 0.14Wilcoxon (Mann-Whitney)
Secondary
Neonatal Length of NICU and Total Hospital Stay Assessed as Number of Days
Time frame: From birth to discharge form delivery hospital, assessed up to 2 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 17-hydroxyprogesterone Caproate | Neonatal Length of NICU and Total Hospital Stay Assessed as Number of Days | 39 days |
| Castor Oil Injections | Neonatal Length of NICU and Total Hospital Stay Assessed as Number of Days | 50 days |
p-value: 0.16Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Neonatal Grade III - IV Intraventricular Hemorrhage
Time frame: From delivery until neonatal hospital discharge, assessed up to 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 17-hydroxyprogesterone Caproate | Number of Participants With Neonatal Grade III - IV Intraventricular Hemorrhage | 1 Participants |
| Castor Oil Injections | Number of Participants With Neonatal Grade III - IV Intraventricular Hemorrhage | 2 Participants |
p-value: >0.99Chi-squared
Secondary
Number of Participants With Neonatal Necrotizing Enterocolitis
Time frame: From delivery to neonatal discharge, assessed up to 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 17-hydroxyprogesterone Caproate | Number of Participants With Neonatal Necrotizing Enterocolitis | 2 Participants |
| Castor Oil Injections | Number of Participants With Neonatal Necrotizing Enterocolitis | 1 Participants |
p-value: 0.59Chi-squared
Secondary
Number of Participants With Neonatal Respiratory Distress Syndrome
Time frame: From delivery until neonatal hospital discharge, assessed up to 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 17-hydroxyprogesterone Caproate | Number of Participants With Neonatal Respiratory Distress Syndrome | 7 Participants |
| Castor Oil Injections | Number of Participants With Neonatal Respiratory Distress Syndrome | 10 Participants |
p-value: 0.31Chi-squared