SCAN: RCT of Progesterone to Prevent Preterm Birth in Nulliparous Women With a Short Cervix

• Sponsor: The George Washington University Biostatistics Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00439374
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 657
• Locations: 14
• Arms: 2
• Duration (Months): 56
• Patients Per Site: 46.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to see if giving progesterone medication to pregnant women, who have never delivered a baby after 19 weeks of pregnancy and who have a short cervix, lowers the risk of early delivery and improves the health of their baby.

Condition or Disease	Intervention/Treatment	Phase
Preterm Delivery; Cervical Length	Drug: 17 alpha-hydroxyprogesterone caproate; Other: Placebo Oil	Phase 3

Detailed Description

Preterm births, defined as the delivery of a baby less than 37 weeks of gestation, are responsible for the majority of neonatal mortality and morbidities. Studies have shown that a number of risk factors, including never having a baby before and having a short cervix are associated with early delivery. Recently the NICHD did a study in women who were pregnant again after having delivered preterm. It showed that giving 17 alpha-hydroxyprogesterone caproate (17P) medication during pregnancy decreased the chance of delivering another preterm baby by 34%. This placebo-controlled randomized clinical trial will address the primary research question: does treatment with 17P initiated before 23 weeks of gestation prevent delivery prior to 37 weeks in nulliparous women with a singleton gestation who have a short cervix?

Study Design

• Study Type: Interventional
• Actual Enrollment: 657 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Treatment with 17 alpha-hydroxyprogesterone caproate via weekly injections of 250 mg of 17p until 37 weeks gestation or delivery vs. weekly injections of placebo oil until 37 weeks gestation or delivery.Treatment with 17 alpha-hydroxyprogesterone caproate via weekly injections of 250 mg of 17p until 37 weeks gestation or delivery vs. weekly injections of placebo oil until 37 weeks gestation or delivery.
• Masking: Double (Participant, Care Provider)
• Masking Description: Patients and care providers are masked to treatment assignment.
• Primary Purpose: Prevention
• Official Title: A Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Nulliparous Women With a Short Cervix
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 17 alpha-hydroxyprogesterone caproate 250 mg of 17 alpha-hydroxyprogesterone caproate given by weekly injection until 37 weeks gestation or delivery	Drug: 17 alpha-hydroxyprogesterone caproate; Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.; Other Names: 17 AHP
Placebo Comparator: Placebo Placebo oil given by weekly injection until 37 weeks gestation or delivery.	Other: Placebo Oil; Placebo oil is a 250 mg/mL solution of castor oil with benzyl benzoate and benzyl alcohol as a preservative

Outcome Measures

Primary Outcome Measures

1. Number of Participants Delivering Before 37 Weeks Gestation [Delivery before 37 weeks gestation]

   Number of participants delivering before 37 weeks gestation by indication

Secondary Outcome Measures

1. Mean Gestational Age at Delivery [Delivery]

   Mean gestational age at delivery

2. Number of Participants With Preterm Premature Rupture of Membranes [<37 weeks]

3. Number of Participants Who Delivered Before 35 Weeks Gestation [Delivery]

   Delivery before 35 weeks gestation

4. Number of Participants Who Delivered Before 32 Weeks Gestation [Delivery]

   Delivery before 32 weeks gestation

5. Number of Participants Who Delivered Before 28 Weeks Gestation [Delivery]

   Delivery before 28 weeks gestation

6. Number of Participants Who Visited the Hospital Due to Preterm Labor [Between randomization and 37 weeks gestation]

   Number of participants who visited the hospital due to preterm labor before 37 weeks gestation

7. Number of Participants Who Underwent Tocolytic Therapy [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

   Number of participants who underwent tocolytic therapy during pregnancy

8. Number of Participants Who Underwent Corticosteroid Therapy [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

   Number of participants who underwent corticosteroid therapy in pregnancy

9. Number of Participants Who Had a Cerclage Placement [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

   Number of participants who had a cerclage placement

10. Number of Participants Experiencing Gestational Hypertension or Preeclampsia [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

11. Number of Participants With Gestational Diabetes Mellitus [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

12. Number of Participants Experiencing Cholestasis [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

13. Number of Participants Who Experienced Placental Abruption [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

14. Number of Participants Who Experienced Chorioamnionitis [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

15. Number of Participants Who Had Cesarean Delivery [delivery]

16. Number of Participants Who Reported Side Effects [Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks]

    Number of participants who reported any side effect, nausea, urticaria, and/or an issue at the injection site

17. Number of Participants Meeting the Composite Adverse Perinatal Outcome and Components [within 72 hours of delivery]

    comprised of fetal or infant death, respiratory distress syndrome, intraventricular hemorrhage (grades 3 and 4), periventricular leukomalacia, necrotizing enterocolitis (stage II and III), Bronchopulmonary dysplasia /chronic lung disease, retinopathy of prematurity (stage III or higher), early onset sepsis

18. Mean Birth Weight [Delivery]

    Birth weight as measured in grams

19. Birth Weight by Count of Participants [Delivery]

    Birth weight by count of participants < 2500 grams and < 1500 grams

20. Number of Neonates Who Measured Small for Gestational Age [Delivery]

    Birth weight percentile and small for gestational age <10th percentile based on number of weeks and gender.

21. Number of Participants With Apgar Score of Less Than 7 at 5 Minutes [5 minutes post delivery]

    The Apgar score is a simple method of quickly assessing the health and vital signs of a newborn baby created by and named after Dr. Virginia Apgar. Apgar testing assesses Appearance, Pulse, Grimace and Activity in a newborn and is typically done at one and five minutes after a baby is born, and it may be repeated at 10, 15, and 20 minutes if the score is low. The five criteria are each scored as 0, 1, or 2 (two being the best), and the total score is calculated by then adding the five values obtained. Agar scores of 0-3 are critically low, 4-6 are below normal, and indicate that the baby likely requires medical intervention, scores of 7+ are considered normal. The lower the Apgar score, the more alert the medical team should be to the possibility of the baby requiring intervention. Some components of the Apgar score are subjective, and there are cases in which a baby requires urgent medical treatment despite having a high Apgar score.

22. Number of Neonates With a Major Congenital Anomaly [Delivery]

    Presence of a major congenital anomaly at birth

23. Number of Neonates With Patent Ductus Arteriosus [Delivery through neonatal discharge]

    Number of neonates diagnosed with the heart defect patent ductus arteriosus

24. Number of Neonates Experiencing Seizures [Delivery through neonatal discharge]

    Number of neonates experiencing seizures from delivery to hospital discharge

25. Number of Neonates Admitted to NICU [Delivery through hospital discharge]

    Admission to the neonatal intensive care unit

26. Median Length of NICU Stay [NICU admission through NICU discharge]

    Median length of stay in the neonatal intensive care unit in days

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Nulliparous

• Cervical length as measured on transvaginal examination < 30mm between gestational ages of 16 weeks 0 days to 22 weeks 3 days

• Gestational age 16 weeks 3 days to 22 weeks 6 days at time of randomization

Exclusion Criteria:

• Multifetal gestation

• Progesterone treatment after 14 weeks 6 days during current pregnancy

• Vaginal bleeding, heavier than spotting, after 15 weeks 6 days

• Amniotic membranes prolapsed beyond external os

• Preterm rupture of membranes

• Fetal anomaly

• Pregnancy without a viable fetus

• Current or planned cervical cerclage

• Congenital Mullerian abnormality of the uterus

• Contraindication to intra-muscular injections

• Hypertension requiring medication

• Diabetes managed with insulin or oral hypoglycemic agents

• DES exposure

• Cervical surgery such as cold knife conization

• Planned indicated preterm delivery

• Participation in another interventional study that influences age at delivery

• Participation in this trial in a previous pregnancy

• Prenatal care or delivery planned outside a MFMU Network center

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Birmingham	Birmingham	Alabama	United States	35429
2	Northwestern University-Prentice Hospital	Chicago	Illinois	United States	60611
3	Dept of OB/GYN, Hutzel Hospital	Detroit	Michigan	United States	48201
4	Columbia University-St. Luke's Hospital	New York	New York	United States	10032
5	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599
6	Case Western Reserve-Metrohealth	Cleveland	Ohio	United States	44109
7	Ohio State University Hospital	Columbus	Ohio	United States	43210
8	Oregon Health & Sciences University	Portland	Oregon	United States	97239
9	University of Pittsburgh-Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
10	Brown University -Women and Infants Hospital	Providence	Rhode Island	United States	02095
11	Dept of OB/GYN, Southwestern Medical Center, University of Texas	Dallas	Texas	United States	75235-9032
12	University of Texas Medical Branch - Galveston	Galveston	Texas	United States	77555
13	University of Texas-Houston	Houston	Texas	United States	77030
14	University of Utah Medical Center	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• The George Washington University Biostatistics Center
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: William Grobman, MD, MBA, Northwestern University
• Study Director: Menachem Miodovnik, MD, NICHD Project Scientist

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about the SCAN protocol

Publications

None provided.

• Responsible Party: The George Washington University Biostatistics Center
• ClinicalTrials.gov Identifier: NCT00439374
• Other Study ID Numbers: HD36801 SCAN; U10HD021410; U10HD027869; U10HD027917; U10HD053097; U10HD027915; U10HD034116; U10HD034208; U10HD034136; U10HD040500; U10HD040485; U10HD040544; U10HD040545; U10HD040560; U10HD040512; U10HD036801; U10HD053118
• First Posted: Feb 23, 2007
• Last Update Posted: Jul 15, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by The George Washington University Biostatistics Center: nulliparous; pregnancy; short cervix; progesterone
• Additional relevant MeSH terms: Premature Birth; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone

Study Results

Participant Flow

Recruitment Details	From April 2007 through May 2011, the fourteen centers of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development participated in this randomized double-blind placebo-controlled trial. Eligible women were offered participation.
Pre-assignment Detail	Women who signed informed consent received a "compliance" injection of the placebo and were asked to return at least 3 days later for randomization. If a woman did not return for a randomization visit before 23 weeks 0 days of gestation, she was excluded.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Period Title: Overall Study
STARTED	327	330
COMPLETED	327	330
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo	Total
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil	Total of all reporting groups
Overall Participants	327	330	657
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.8 (5.3)	21.6 (4.4)	22.2 (4.9)
Sex: Female, Male (Count of Participants)
Female	327 100%	330 100%	657 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic white	76 23.2%	74 22.4%	150 22.8%
Non-hispanic black	179 54.7%	161 48.8%	340 51.8%
Hispanic white	19 5.8%	38 11.5%	57 8.7%
Hispanic black	2 0.6%	0 0%	2 0.3%
Asian	4 1.2%	3 0.9%	7 1.1%
Other	47 14.4%	54 16.4%	101 15.4%
Prepregnancy body mass index (kg^m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg^m2]	26.1 (6.9)	25.4 (6.5)	25.7 (6.7)
Prior Pregnancy (Count of Participants)
<13 wk of gestation	92 28.1%	82 24.8%	174 26.5%
13-19 wk of gestation	13 4%	10 3%	23 3.5%
Payment for obstetric care (Count of Participants)
Uninsured/self-pay	17 5.2%	30 9.1%	47 7.2%
Private insurance	74 22.6%	62 18.8%	136 20.7%
Government-assisted insurance	236 72.2%	238 72.1%	474 72.1%
Married or living with partner (Count of Participants)
Count of Participants [Participants]	125 38.2%	110 33.3%	235 35.8%
Alcohol use during pregnancy (Count of Participants)
Count of Participants [Participants]	33 10.1%	20 6.1%	53 8.1%
Smoking during pregnancy (Count of Participants)
Count of Participants [Participants]	48 14.7%	62 18.8%	110 16.7%
Illicit substance use during pregnancy (Count of Participants)
Count of Participants [Participants]	15 4.6%	24 7.3%	39 5.9%
Gestational age at randomization (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	21.4 (1.2)	21.3 (1.3)	21.4 (1.3)
Cervical length at screening (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	23.9 (5.6)	23.8 (5.7)	23.8 (5.7)
Cervical length at screening <15mm (Count of Participants)
Count of Participants [Participants]	25 7.6%	31 9.4%	56 8.5%
Cervical funnel present (Count of Participants)
Count of Participants [Participants]	88 26.9%	69 20.9%	157 23.9%
Cervical funnel length (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	14.8 (8.0)	16.7 (8.7)	15.6 (8.4)
Debris present (Count of Participants)
Count of Participants [Participants]	39 11.9%	39 11.8%	78 11.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Delivering Before 37 Weeks Gestation
Description	Number of participants delivering before 37 weeks gestation by indication
Time Frame	Delivery before 37 weeks gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Total Delivery <37 wk	82 25.1%	80 24.2%
Spontaneous	54 16.5%	55 16.7%
Medically indicated	27 8.3%	25 7.6%
Fetal loss/abortion <20 wk	1 0.3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	All deliveries less than 37 weeks
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Spontaneous deliveries
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Medically-indicated deliveries
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Gestational Age at Delivery
Description	Mean gestational age at delivery
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Mean (Standard Deviation) [weeks]	37.6 (3.9)	37.4 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Number of Participants With Preterm Premature Rupture of Membranes
Time Frame	<37 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Count of Participants [Participants]	25 7.6%	24 7.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants Who Delivered Before 35 Weeks Gestation
Description	Delivery before 35 weeks gestation
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Count of Participants [Participants]	44 13.5%	53 16.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants Who Delivered Before 32 Weeks Gestation
Description	Delivery before 32 weeks gestation
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Count of Participants [Participants]	28 8.6%	32 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants Who Delivered Before 28 Weeks Gestation
Description	Delivery before 28 weeks gestation
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Count of Participants [Participants]	15 4.6%	22 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.36 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants Who Visited the Hospital Due to Preterm Labor
Description	Number of participants who visited the hospital due to preterm labor before 37 weeks gestation
Time Frame	Between randomization and 37 weeks gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Count of Participants [Participants]	145 44.3%	151 45.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants Who Underwent Tocolytic Therapy
Description	Number of participants who underwent tocolytic therapy during pregnancy
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 6 participants in the treatment group and 5 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	321	325
Count of Participants [Participants]	35 10.7%	42 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants Who Underwent Corticosteroid Therapy
Description	Number of participants who underwent corticosteroid therapy in pregnancy
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 6 participants in the treatment group and 5 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	321	325
Count of Participants [Participants]	55 16.8%	51 15.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Participants Who Had a Cerclage Placement
Description	Number of participants who had a cerclage placement
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 6 participants in the treatment group and 5 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	321	325
Count of Participants [Participants]	6 1.8%	4 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.52
	Confidence Interval	(2-Sided) 95%; 0.43 to 5.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Number of Participants Experiencing Gestational Hypertension or Preeclampsia
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 1 participant in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	329
Count of Participants [Participants]	46 14.1%	40 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants With Gestational Diabetes Mellitus
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Count of Participants [Participants]	15 4.6%	13 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.56 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants Experiencing Cholestasis
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 1 participant in the Placebo group

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	329
Count of Participants [Participants]	1 0.3%	0 0%

14. Secondary Outcome

Title	Number of Participants Who Experienced Placental Abruption
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	328
Count of Participants [Participants]	11 3.4%	15 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.34 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Number of Participants Who Experienced Chorioamnionitis
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	328
Count of Participants [Participants]	29 8.9%	20 6.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.84 to 2.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Number of Participants Who Had Cesarean Delivery
Time Frame	delivery

Outcome Measure Data

Analysis Population Description

Data was missing for 1 participant in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	329
Count of Participants [Participants]	67 20.5%	63 19.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Number of Participants Who Reported Side Effects
Description	Number of participants who reported any side effect, nausea, urticaria, and/or an issue at the injection site
Time Frame	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data was missing for 1 participant in the treatment group and 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	326	328
Any	223 68.2%	220 66.7%
Injection site	217 66.4%	209 63.3%
Urticaria	10 3.1%	2 0.6%
Nausea	7 2.1%	10 3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Any side effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Injection site
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Urticaria
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	5.03
	Confidence Interval	(2-Sided) 95%; 1.11 to 22.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Nausea
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.27 to 1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Number of Participants Meeting the Composite Adverse Perinatal Outcome and Components
Description	comprised of fetal or infant death, respiratory distress syndrome, intraventricular hemorrhage (grades 3 and 4), periventricular leukomalacia, necrotizing enterocolitis (stage II and III), Bronchopulmonary dysplasia /chronic lung disease, retinopathy of prematurity (stage III or higher), early onset sepsis
Time Frame	within 72 hours of delivery

Outcome Measure Data

Analysis Population Description

With the exception of the composite outcome and death, the neonatal outcomes were only measured for live births.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Composite Outcome Total	23 7%	30 9.1%
Fetal Death	4 1.2%	1 0.3%
Neonatal Death	6 1.8%	8 2.4%
Respiratory Distress Syndrome	13 4%	16 4.8%
Bronchopulmonary dysplasia	3 0.9%	5 1.5%
Necrotizing enterocolitis, grade II or III	2 0.6%	5 1.5%
Intraventricular Hemorrhage, Grade III or IV	2 0.6%	1 0.3%
Periventricular Leukomalacia	4 1.2%	1 0.3%
Early-onset Sepsis	3 0.9%	11 3.3%
Retinopathy of prematurity, grade II or IV	1 0.3%	3 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments	Analysis is for the total composite
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Mean Birth Weight
Description	Birth weight as measured in grams
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	327	330
Mean (Standard Deviation) [Grams]	2855 (747)	2824 (807)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

20. Secondary Outcome

Title	Birth Weight by Count of Participants
Description	Birth weight by count of participants < 2500 grams and < 1500 grams
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

Data was missing for 4 participants in the treatment group and 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	323	328
Birth weight < 2500g	72 22%	75 22.7%
Birth weight < 1500g	23 7%	29 8.8%

21. Secondary Outcome

Title	Number of Neonates Who Measured Small for Gestational Age
Description	Birth weight percentile and small for gestational age <10th percentile based on number of weeks and gender.
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

Data was missing for 4 participants in the treatment group and 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	323	328
< 10th percentile	54 16.5%	47 14.2%
< 3rd percentile	15 4.6%	14 4.2%

22. Secondary Outcome

Title	Number of Participants With Apgar Score of Less Than 7 at 5 Minutes
Description	The Apgar score is a simple method of quickly assessing the health and vital signs of a newborn baby created by and named after Dr. Virginia Apgar. Apgar testing assesses Appearance, Pulse, Grimace and Activity in a newborn and is typically done at one and five minutes after a baby is born, and it may be repeated at 10, 15, and 20 minutes if the score is low. The five criteria are each scored as 0, 1, or 2 (two being the best), and the total score is calculated by then adding the five values obtained. Agar scores of 0-3 are critically low, 4-6 are below normal, and indicate that the baby likely requires medical intervention, scores of 7+ are considered normal. The lower the Apgar score, the more alert the medical team should be to the possibility of the baby requiring intervention. Some components of the Apgar score are subjective, and there are cases in which a baby requires urgent medical treatment despite having a high Apgar score.
Time Frame	5 minutes post delivery

Outcome Measure Data

Analysis Population Description

Data was missing for 4 participants in the treatment group and 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	323	328
Count of Participants [Participants]	15 4.6%	19 5.8%

23. Secondary Outcome

Title	Number of Neonates With a Major Congenital Anomaly
Description	Presence of a major congenital anomaly at birth
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

Data was missing for 1 participant in the treatment group and 2 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	326	328
Count of Participants [Participants]	6 1.8%	2 0.6%

24. Secondary Outcome

Title	Number of Neonates With Patent Ductus Arteriosus
Description	Number of neonates diagnosed with the heart defect patent ductus arteriosus
Time Frame	Delivery through neonatal discharge

Outcome Measure Data

Analysis Population Description

Data was missing for 7 participants in the treatment group and 8 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	320	322
Count of Participants [Participants]	2 0.6%	8 2.4%

25. Secondary Outcome

Title	Number of Neonates Experiencing Seizures
Description	Number of neonates experiencing seizures from delivery to hospital discharge
Time Frame	Delivery through neonatal discharge

Outcome Measure Data

Analysis Population Description

Data was missing for 7 participants in the treatment group and 8 participants in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	320	322
Count of Participants [Participants]	1 0.3%	2 0.6%

26. Secondary Outcome

Title	Number of Neonates Admitted to NICU
Description	Admission to the neonatal intensive care unit
Time Frame	Delivery through hospital discharge

Outcome Measure Data

Analysis Population Description

Data was missing for 5 participants in the treatment group and 1 participant in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	322	329
Count of Participants [Participants]	63 19.3%	69 20.9%

27. Secondary Outcome

Title	Median Length of NICU Stay
Description	Median length of stay in the neonatal intensive care unit in days
Time Frame	NICU admission through NICU discharge

Outcome Measure Data

Analysis Population Description

Data was missing for 5 participants in the treatment group and 1 participant in the placebo group.

Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate	Placebo
Arm/Group Description	17 alpha-hydroxyprogesterone caproate 17 alpha-hydroxyprogesterone caproate : Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.	castor oil
Measure Participants	322	329
Median (Inter-Quartile Range) [days]	17	15.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17 Alpha-hydroxyprogesterone Caproate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse event data was collected during the study period of April 2007 through June 2010, from the time of the participants randomization through hospital discharge of the mother and baby (up to 60 days).
Adverse Event Reporting Description	Other adverse events that are related to side effects are available for patients who had at least 1 study visit. 1 randomized participant in the treatment group and 2 randomized participants in the placebo group did not attend a study visit after randomization. Therefore the Ns for other side effects are different than those for the serious adverse events and the study sample (by 3 participants total).
Arm/Group Title	17 Alpha-hydroxyprogesterone Caproate		Placebo
Arm/Group Description	250 mg of 17 alpha-hydroxyprogesterone caproate given by weekly injection until 37 weeks gestation or delivery 17 alpha-hydroxyprogesterone caproate: Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.		Placebo oil given by weekly injection until 37 weeks gestation or delivery. Placebo Oil: Placebo oil is a 250 mg/mL solution of castor oil with benzyl benzoate and benzyl alcohol as a preservative
All Cause Mortality
	17 Alpha-hydroxyprogesterone Caproate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	17 Alpha-hydroxyprogesterone Caproate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/327 (6.7%)		13/330 (3.9%)
Blood and lymphatic system disorders
Maternal blood disorders	2/327 (0.6%)		0/330 (0%)
Neonatal Hematochromatosis	1/327 (0.3%)		0/330 (0%)
Cardiac disorders
Maternal Pulmonary edema	1/327 (0.3%)		0/330 (0%)
Congenital, familial and genetic disorders
Congenital Anomalies	5/327 (1.5%)		3/330 (0.9%)
General disorders
Neonatal death	6/327 (1.8%)		8/330 (2.4%)
Pregnancy, puerperium and perinatal conditions
Miscarriage or stillbirth	5/327 (1.5%)		1/330 (0.3%)
Placental abruption	2/327 (0.6%)		2/330 (0.6%)
Pregnancy Complications	3/327 (0.9%)		3/330 (0.9%)
Vascular disorders
Chest Pain	1/327 (0.3%)		0/330 (0%)
Epistaxis	1/327 (0.3%)		0/330 (0%)
Other (Not Including Serious) Adverse Events
	17 Alpha-hydroxyprogesterone Caproate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	326/326 (100%)		328/328 (100%)
Gastrointestinal disorders
Nausea	7/326 (2.1%)		10/328 (3%)
Vomiting	6/326 (1.8%)		3/328 (0.9%)
Diarrhea	2/326 (0.6%)		6/328 (1.8%)
General disorders
Headache	7/326 (2.1%)		8/328 (2.4%)
Fatigue	5/326 (1.5%)		2/328 (0.6%)
Skin and subcutaneous tissue disorders
Reaction at injection site	217/326 (66.6%)		210/328 (64%)
Sore/burn at injection site	145/326 (44.5%)		153/328 (46.6%)
Itching at injection site	121/326 (37.1%)		109/328 (33.2%)
Swelling/lump at injection site	107/326 (32.8%)		93/328 (28.4%)
Bruising at injection site	26/326 (8%)		23/328 (7%)
Redness at injection site	8/326 (2.5%)		11/328 (3.4%)
Urticaria	10/326 (3.1%)		2/328 (0.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.