SAFER: Sleep Apnea and Fetal Growth Restriction

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04084990
• Collaborator: ResMed Foundation (Other), The Hebrew University Hadassah Medical School (Other), University of Rochester (Other)
• Enrollment: 3
• Locations: 3
• Arms: 2
• Actual Duration (Months): 20.3
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study aims to evaluate the association between obstructive sleep apnea (OSA) and fetal growth restriction (FGR) and to assess the role of auto-titrated positive airway pressure (aPAP) as antenatal therapy in these patients. Pregnant patients with diagnosed FGR will be screened for OSA first by screening questionnaire and then by home sleep monitor. Of those patients diagnosed with OSA, half will be assigned to use aPAP each night when sleeping and half will not (standard care).

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea; Fetal Growth Restriction; Pregnancy Related	Device: S9 VPAP Adapt	Phase 3

Detailed Description

Fetal growth restriction (FGR) affects 5-10% of pregnancies and is one of the leading causes of perinatal morbidity and mortality.

Obstructive sleep apnea (OSA) is a common disorder in which a person's breathing pauses or becomes shallow during sleep. These periods of low oxygen lead stress and inflammation which that may be harmful to both the mother and her fetus. OSA in pregnancy has been associated with poor maternal-fetal outcomes, including low birth weight, preterm delivery, FGR, gestational hypertension/preeclampsia, gestational diabetes and higher rates of neonatal ICU admission.

Auto-titrated positive airway pressure (aPAP) is a machine that gently delivers pressurized air via a mask to keep a patient's airways free of obstruction during sleep. It is currently unclear whether treatment of OSA during pregnancy in women with known FGR can improve fetal and neonatal outcomes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, parallel group, investigator-blinded, randomized controlled trialProspective, parallel group, investigator-blinded, randomized controlled trial
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Sleep Apnea and Fetal Growth Restriction
• Actual Study Start Date: Nov 18, 2019
• Actual Primary Completion Date: Jul 27, 2021
• Actual Study Completion Date: Jul 27, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: aPAP Nightly use of aPAP when sleeping through the date of delivery	Device: S9 VPAP Adapt; Auto-titrated positive airway pressure
No Intervention: No aPAP No use of aPAP (standard of care)

Outcome Measures

Primary Outcome Measures

1. Birth Weight [1 day]

   Weight of child at time of birth

Secondary Outcome Measures

1. Gestational Age at Delivery [1 day]

   Gestational age at delivery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 18 and ≤ 50

• Fetal growth restriction (defined as fetal weight <10th percentile based on at least one routine 2nd trimester ultrasound without a subsequent increase to >15th percentile on any ultrasounds prior to enrollment)

• Lower limit of gestational age at enrollment 22+0 weeks.

• Upper limit of gestational age at enrollment: adequate time to complete Stages 1 and 2 and if appropriate to be randomized and receive intervention by no later than 32+0 weeks.

• The absence of 2 minor or 1 major markers of aneuploidy.

Exclusion Criteria:

• Other known cause of fetal growth restriction (including congenital anomalies, intrauterine infection, or multiple gestation)

• Reversed end-diastolic flow in the umbilical artery

• Preexisting diagnosis of OSA being treated with aPAP

• Chronic pulmonary disease (cystic fibrosis, moderate persistent asthma)

• Hemoglobinopathies (sickle cell anemia, thalassemia)

• Maternal craniofacial anomalies

• Premature rupture of membranes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
2	Rochester University Medical Center	Rochester	New York	United States	14620
3	Hadassah Hebrew University	W. Jerusalem	Jerusalem	Israel	9112001

Sponsors and Collaborators

• Washington University School of Medicine
• ResMed Foundation
• The Hebrew University Hadassah Medical School
• University of Rochester

Investigators

• Principal Investigator: Alexander Hincker, MD, Washington University in Saint Louis

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 21, 2021
• Informed Consent Form - Jul 21, 2021

More Information

Publications

• Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia--revisited--the bad ugly and good: implications to the heart and brain. Sleep Med Rev. 2015 Apr;20:27-45. doi: 10.1016/j.smrv.2014.07.003. Epub 2014 Jul 24. Review.
• Nardozza LM, Caetano AC, Zamarian AC, Mazzola JB, Silva CP, Marçal VM, Lobo TF, Peixoto AB, Araujo Júnior E. Fetal growth restriction: current knowledge. Arch Gynecol Obstet. 2017 May;295(5):1061-1077. doi: 10.1007/s00404-017-4341-9. Epub 2017 Mar 11. Review.

• Responsible Party: Alexander M. Hincker, Assistant Professor, Department of Anesthesiology, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT04084990
• Other Study ID Numbers: 201908162
• First Posted: Sep 11, 2019
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Alexander M. Hincker, Assistant Professor, Department of Anesthesiology, Washington University School of Medicine: aPAP; OSA; FGR
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Fetal Growth Retardation

Study Results

Participant Flow

Recruitment Details

The study has been terminated due to low enrollment after only 3 participants were randomized. Results will not be analyzed owing to the small number of participants to be randomized to receive aPAP (the intervention) or no aPAP (standard of care treatment).

Pre-assignment Detail

32 participants provided informed consent to participate. They underwent an obstructive sleep apnea (OSA) risk assessment questionnaire. Those screening as high risk for OSA underwent home sleep apnea testing (HSAT). Those screening as positive on the HSAT, which was defined as an apnea hypopnea index (AHI) >= 10 OR an AHI >= 5 with oxygen desaturation index >= 5, were randomized to receive aPAP or not. Of the 32 participants, only 3 met criteria for enrollment in the randomization phase.

Arm/Group Title	aPAP	No aPAP
Arm/Group Description	Nightly use of aPAP when sleeping through the date of delivery S9 VPAP Adapt: Auto-titrated positive airway pressure	No use of aPAP (standard of care)
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	aPAP	No aPAP	Total
Arm/Group Description	Nightly use of aPAP when sleeping through the date of delivery S9 VPAP Adapt: Auto-titrated positive airway pressure	No use of aPAP (standard of care)	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	32.8	29.8	31.8
Sex: Female, Male (Count of Participants)
Female	2 100%	1 100%	3 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 50%	0 0%	1 33.3%
Not Hispanic or Latino	1 50%	1 100%	2 66.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 50%	1 100%	2 66.7%
White	1 50%	0 0%	1 33.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Birth Weight
Description	Weight of child at time of birth
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

Of two mothers randomized to aPAP therapy, one required pre-term induction of labor for maternal safety for preeclampsia with severe features. This fetus experienced in-utero fetal demise, so birth weight was not obtained.

Arm/Group Title	aPAP	No aPAP
Arm/Group Description	Nightly use of aPAP when sleeping through the date of delivery S9 VPAP Adapt: Auto-titrated positive airway pressure	No use of aPAP (standard of care)
Measure Participants	1	1
Mean (Full Range) [grams]	2320	570

2. Secondary Outcome

Title	Gestational Age at Delivery
Description	Gestational age at delivery
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aPAP	No aPAP
Arm/Group Description	Nightly use of aPAP when sleeping through the date of delivery S9 VPAP Adapt: Auto-titrated positive airway pressure	No use of aPAP (standard of care)
Measure Participants	2	1
Mean (Full Range) [weeks (estimated gestational age)]	31.4	25.7

Adverse Events

Time Frame	Approximately 9.5 months
Arm/Group Title	aPAP		No aPAP
Arm/Group Description	Nightly use of aPAP when sleeping through the date of delivery S9 VPAP Adapt: Auto-titrated positive airway pressure		No use of aPAP (standard of care)
All Cause Mortality
	aPAP		No aPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	aPAP		No aPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	aPAP		No aPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.