17OHP-C Dosing Among Obese Pregnant Women

• Sponsor: University of South Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT03433040
• Collaborator: Washington University School of Medicine (Other)
• Enrollment: 44
• Locations: 2
• Arms: 3
• Actual Duration (Months): 46.7
• Patients Per Site: 22
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Emergency data suggest 17OHP-C may be less efficacious in obese women. Since obesity is associated with lower levels of plasma 17OHP-C, the investigator hypothesize that higher doses of 17OHP-C may help to prevent spontaneous PTB among obese women. The study aims to compare the pharmacokinetics of 17 OHP-C in obese compared with non-obese women.

Condition or Disease	Intervention/Treatment	Phase
Premature Birth; Absorption; Chemicals	Drug: 17-Hydroxyprogesterone Capronate	Phase 3

Detailed Description

Prospective three arm study of women with a prior spontaneous PTB. Non-obese women will receive the standard 250 mg weekly dose of 17 OHP-C while obese women will be randomly assigned to the standard (250 mg) or higher dose (500 mg). The resulting three groups will consist of:

1. Normal weight women on 250mg 17OHPC

2. Obese women on 250mg 17OHPC

3. Obese women on 500mg of 17OHPC

Initial Enrollment: Pregnant patients receiving prenatal care at one of the USF affiliated sites or Washington University in St. Louis sites who report a history of a PTB will be approached by the research nurse. The research nurse will explain the study, review inclusion/exclusion criteria with the patient, and invite interested potential study candidates to sign a medical records release so that records from the previous PTB can be reviewed. If the medical records confirm the birth of a previous PTB was of a live born singleton gestation between the gestational ages of 20 weeks and 36 weeks and 6 days then the patient will be invited to participate in the study. At that time the informed consent form will be thoroughly reviewed with the patient, and if the patient desires to enroll, the patient will provide informed consent to enroll in the study. Consecutive women with normal BMI or obese women meeting the inclusion criteria will be approached to avoid selection bias.

Randomization: will occur at the time of enrollment. The randomization will be computer generated. Randomization envelopes indicating the randomization arm will be prepared ahead of time and the next consecutive envelope will be used at time of enrollment.

Pharmacokinetic studies: Sampling schedule in order to investigate the pharmacokinetics of 250 mg 17OHP-C weekly as compared to 500 mg 17OHP-C weekly in obese women as well as 250 mg in non-obese women will be performed as follows:

• Using principles described by Caritis et al., four completed weeks of 17OHP-C therapy is required prior to sampling anticipating that steady state will be achieved by this time point.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Impact of a Higher Dose on the Pharmacokinetics of 17-alpha Hydroxyprogesterone Caproate in Obese Women
• Actual Study Start Date: Aug 23, 2017
• Actual Primary Completion Date: Jun 1, 2021
• Actual Study Completion Date: Jul 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: non obese 250mg 17 OHP-C	Drug: 17-Hydroxyprogesterone Capronate; 17-Hydroxyprogesterone Capronate 250mg versus 500mg
Other: obese - control 250mg 17 OHP-C	Drug: 17-Hydroxyprogesterone Capronate; 17-Hydroxyprogesterone Capronate 250mg versus 500mg
Experimental: obese 500mg 17 OHP-C	Drug: 17-Hydroxyprogesterone Capronate; 17-Hydroxyprogesterone Capronate 250mg versus 500mg

Outcome Measures

Primary Outcome Measures

1. Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. [From enrollment to 36 weeks of pregnancy]

   Blood levels

Secondary Outcome Measures

1. Gestational Age at Delivery [Up to 37 weeks]

   Gestational age at delivery in weeks . Too few to dichotomize to <37, 34 and 32 weeks as previously planned.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• • Pregnant women, with a singleton gestation

• Ages 18 - 55

• Able to read and write in English and / or Spanish

• History of spontaneous PTB

• Obesity (≥ 30 kg / m2 ) vs non-obese groups (18 - 29.9 kg / m2 ) defined by first documented body mass index at an office visit

• Gestational age between 12 weeks, 0 days and 24 weeks, 6 days of gestation

• An ultrasound before 24 + 6 weeks gestation to confirm dating and to rule out major fetal anomalies

• Willing to have weekly injections at the physician's office

• The newborn will be enrolled on the mothers consent for chart review only

https://register.clinicaltrials.gov/prs/html/definitions.html?popup=true#Eligibility

Exclusion Criteria:

• • Multifetal gestation

• Known fetal anomaly

• Current progesterone treatment

• Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions

• Current or history of thrombosis or thromboembolic disorder

• Current anticoagulation

• Undiagnosed abnormal vaginal bleeding unrelated to pregnancy

• Cholestatic jaundice of pregnancy

• Liver tumors, benign or malignant, or active liver disease

• uncontrolled hypertension (controlled hypertension is eligible)

• A seizure disorder

• Current or planned cervical cerclage

• Plan to deliver elsewhere

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Florida	Tampa	Florida	United States	33606
2	Washington University in St Louis	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• University of South Florida
• Washington University School of Medicine

Investigators

• Principal Investigator: Anthony O Odibo, MD, University of South Florida

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 2, 2021

More Information

Publications

None provided.

• Responsible Party: Anthony Odibo MD, Director Ultrasound and Fetal Therapy, University of South Florida
• ClinicalTrials.gov Identifier: NCT03433040
• Other Study ID Numbers: 00026055
• First Posted: Feb 14, 2018
• Last Update Posted: Jan 12, 2022
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Premature Birth; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone

Study Results

Participant Flow

Arm/Group Title	Non Obese	Obese - Control	Obese
Arm/Group Description	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	500mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg
Period Title: Overall Study
STARTED	19	16	9
COMPLETED	17	8	5
NOT COMPLETED	2	8	4

Baseline Characteristics

Arm/Group Title	Non Obese	Obese - Control	Obese	Total
Arm/Group Description	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	500mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	Total of all reporting groups
Overall Participants	17	8	5	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	17 100%	8 100%	5 100%	30 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.2 (5.1)	31.6 (6.4)	31.4 (4.6)	31.7 (5.2)
Sex: Female, Male (Count of Participants)
Female	17 100%	8 100%	5 100%	30 100%
Male	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 5.9%	0 0%	0 0%	1 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	7 41.2%	4 50%	4 80%	15 50%
White	9 52.9%	4 50%	1 20%	14 46.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Number) [Number]
United States	17 100%	8 100%	5 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks.
Description	Blood levels
Time Frame	From enrollment to 36 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non Obese	Obese - Control	Obese
Arm/Group Description	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	500mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg
Measure Participants	17	8	5
20-22 weeks	10.1 (4.5)	13.0 (5.1)	18.0 (6.7)
27-29 weeks	11.5 (4.8)	8.1 (5.6)	17.9 (2.5)
34-36 weeks	15.2 (12.5)	11.1 (6.2)	24.6 (7.1)

2. Secondary Outcome

Title	Gestational Age at Delivery
Description	Gestational age at delivery in weeks . Too few to dichotomize to <37, 34 and 32 weeks as previously planned.
Time Frame	Up to 37 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non Obese	Obese - Control	Obese
Arm/Group Description	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg	500mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg
Measure Participants	17	8	5
Mean (Standard Deviation) [Weeks]	36.7 (2.6)	38.4 (1.4)	32.2 (5.5)

Adverse Events

Time Frame	6 months
Arm/Group Title	Non Obese		Obese - Control		Obese
Arm/Group Description	250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg		250mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg		500mg 17 OHP-C 17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg
All Cause Mortality
	Non Obese		Obese - Control		Obese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/8 (0%)		0/5 (0%)
Serious Adverse Events
	Non Obese		Obese - Control		Obese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/8 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Non Obese		Obese - Control		Obese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/8 (0%)		0/5 (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.