Progesterone for the Management of Preterm, Premature Rupture of the Membranes: A Randomized Controlled Trial.

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01050647
• Collaborator: (none)
• Enrollment: 21
• Locations: 2
• Arms: 2
• Duration (Months): 69.9
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Complications	Drug: 17-Hydroxyprogesterone Caproate; Other: Caster Oil injections	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Progesterone for the Management of Preterm, Premature Rupture of the Membranes: A Randomized Controlled Trial.
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 17-hydroxyprogesterone caproate Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation	Drug: 17-Hydroxyprogesterone Caproate; Weekly injections of 17-hydroxyprogesterone caproate.; Other Names: Active study drug
Placebo Comparator: Castor oil injections Weekly injections of Caster Oil (placebo)	Other: Caster Oil injections; Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Number of Participants With Neonatal Respiratory Distress Syndrome [From delivery until neonatal hospital discharge, assessed up to 2 months]

2. Number of Participants With Neonatal Grade III - IV Intraventricular Hemorrhage [From delivery until neonatal hospital discharge, assessed up to 2 months]

3. Number of Participants With Neonatal Necrotizing Enterocolitis [From delivery to neonatal discharge, assessed up to 2 months]

4. 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]

5. Length of Latency Assessed as Number of Days [From rupture of membranes until delivery, assessed up to 34 weeks of gestation]

Eligibility Criteria

Criteria

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

2. Evidence of active infection

3. Evidence of significant placental abruption

4. IUFD diagnosed at the time of P-PROM diagnosis

5. Major fetal malformation

6. Maternal allergy to progesterone or placebo drug components

7. Current use of progesterone at the time of P-PROM

8. Multiple Gestations

9. Inability to understand consent in either English or Spanish

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Santa Clara Valley Medical Center	San Jose	California	United States	95128
2	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Yasser Y El-Sayed, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yasser Yehia El-Sayed, Professor of Obstetrics and Gynecology, Stanford University
• ClinicalTrials.gov Identifier: NCT01050647
• Other Study ID Numbers: SU-01082010-4683; 17976
• First Posted: Jan 15, 2010
• Last Update Posted: Apr 9, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Pregnancy Complications; Rupture; Castor Oil; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone

Study Results

Participant Flow

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Period Title: Overall Study
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections	Total
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.7 (1.9)	31.7 (2.0)	31.7 (1.95)
Sex: Female, Male (Count of Participants)
Female	10 100%	11 100%	21 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 70%	8 72.7%	15 71.4%
Not Hispanic or Latino	3 30%	2 18.2%	5 23.8%
Unknown or Not Reported	0 0%	1 9.1%	1 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 10%	0 0%	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 10%	0 0%	1 4.8%
White	5 50%	6 54.5%	11 52.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 30%	5 45.5%	8 38.1%
Region of Enrollment (Count of Participants)
United States	10 100%	11 100%	21 100%
History of prior preterm birth (Count of Participants)
Count of Participants [Participants]	3 30%	0 0%	3 14.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Achievement of 34 Weeks Gestation
Description	Delayed delivery until 34 weeks gestation.
Time Frame	From enrollment until delivery, an average of 34 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Measure Participants	10	11
Count of Participants [Participants]	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Neonatal Respiratory Distress Syndrome
Time Frame	From delivery until neonatal hospital discharge, assessed up to 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Measure Participants	10	11
Count of Participants [Participants]	7 70%	10 90.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17-hydroxyprogesterone Caproate, Castor Oil Injections
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Number of Participants With Neonatal Grade III - IV Intraventricular Hemorrhage
Time Frame	From delivery until neonatal hospital discharge, assessed up to 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Measure Participants	10	11
Count of Participants [Participants]	1 10%	2 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17-hydroxyprogesterone Caproate, Castor Oil Injections
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Number of Participants With Neonatal Necrotizing Enterocolitis
Time Frame	From delivery to neonatal discharge, assessed up to 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Measure Participants	10	11
Count of Participants [Participants]	2 20%	1 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17-hydroxyprogesterone Caproate, Castor Oil Injections
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Measure Participants	10	11
Mean (95% Confidence Interval) [days]	39	50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17-hydroxyprogesterone Caproate, Castor Oil Injections
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Length of Latency Assessed as Number of Days
Time Frame	From rupture of membranes until delivery, assessed up to 34 weeks of gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	17-hydroxyprogesterone Caproate	Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.	Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
Measure Participants	10	11
Median (95% Confidence Interval) [days]	14.5	8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	17-hydroxyprogesterone Caproate, Castor Oil Injections
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	From enrollment up to discharge from the delivery hospital, assessed up to 2 months after delivery
Arm/Group Title	17-hydroxyprogesterone Caproate		Castor Oil Injections
Arm/Group Description	Weekly injections of 17-hydroxyprogesterone caproate until patient reached 34 completed weeks of gestation 17-Hydroxyprogesterone Caproate: Weekly injections of 17-hydroxyprogesterone caproate.		Weekly injections of Caster Oil (placebo) Caster Oil injections: Weekly injection of Caster Oil (Placebo) until patient reached 34 weeks gestation.
All Cause Mortality
	17-hydroxyprogesterone Caproate		Castor Oil Injections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Serious Adverse Events
	17-hydroxyprogesterone Caproate		Castor Oil Injections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	17-hydroxyprogesterone Caproate		Castor Oil Injections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)

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.