Clinical trial NCT03487185: Continuous Positive Airway Pressure (CPAP) for Sleep Apnea in Pregnancy
Official title: A Randomized Trial of Continuous Positive Airway Pressure (CPAP) for Sleep Apnea in Pregnancy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obstructive Sleep Apnea of Adult
Preeclampsia
Obstetrical Complications
Keywords: CPAP
Apnea
pregnancy
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-04-03
Enrollment: 1500
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Women who are between 14 weeks 0 days and 21 weeks 5 days with a singleton gestation and obstructive sleep apnea (OSA) will be randomized to one of two arms at participating MFMU Network clinical center:

* Autotitrating CPAP with weekly contact, incentives for compliance and initial sleep advice counseling
* Initial sleep advice counseling alone
Primary purpose: PREVENTION

Brief summary: A randomized controlled trial of 1,500 women to assess whether treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in pregnancy will result in a reduction in the rate of hypertensive disorders of pregnancy.

Detailed description: Emerging data support a link between sleep disordered breathing (SDB) and adverse pregnancy outcomes. In particular, women with obstructive sleep apnea (OSA) appear to be at increased risk of both hypertensive disorders of pregnancy and gestational diabetes. In the non-pregnant population, OSA is typically treated with continuous positive airway pressure (CPAP) during sleep and has been shown to reduce blood pressure in hypertensive patients. Unfortunately, data on whether maternal and neonatal outcomes could be improved with treatment of OSA during pregnancy are extremely limited. This study aims to address this knowledge gap.

A randomized controlled trial of 1,500 women to assess whether treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in pregnancy will result in a reduction in the rate of hypertensive disorders of pregnancy.

Eligibility criteria: Inclusion Criteria

1. Singleton gestation. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks project gestational age.
2. Gestational age at randomization between 14 weeks 0 days and 21 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
3. Diagnosis with mild to moderate OSA as defined by an AHI score ≥ 5 and \<30.

Exclusion Criteria

1. Previously prescribed, current or planned therapy for sleep apnea.
2. Age \< 18 years, because the rate of sleep apnea in this population is extremely low.
3. Inability to sleep in a stable place with access to the CPAP machine at least 5 nights per week.
4. Asthma requiring systemic steroid therapy for more than 14 days within the past 6 months because this population is expected to be unresponsive to CPAP therapy.
5. Current use of prescribed sleeping pills for insomnia.
6. Chronic medical conditions requiring oxygen supplementation (e.g. pulmonary fibrosis, pulmonary hypertension, cystic fibrosis) because this population is expected to be unresponsive to CPAP therapy.
7. Chronic renal disease with serum creatinine \>1.3 mg/dL because the primary outcome would be pre-determined.
8. Antiphospholipid antibody syndrome, because it would compromise the primary outcome diagnosis.
9. History of medical complications such as:

   1. Active liver disease (acute hepatitis, chronic active hepatitis, persistently abnormal liver enzymes)
   2. Thrombocytopenia with platelet count \<100,000 because of the difficulty in assessing the primary outcome.
10. Active vaginal bleeding (more than spotting) at the time of randomization.
11. Known chromosomal, genetic, major malformations or fetal demise, or planned termination of pregnancy because inclusion would compromise evaluation of secondary neonatal outcomes.
12. Known major uterine malformations associated with adverse pregnancy outcomes.
13. Current use of opiates (heroin, methadone, or other daily opioid use) due to inaccuracy of the home sleep test and inefficiency of CPAP.
14. Active drug use, alcohol use, or unstable psychiatric condition.
15. Participation in another interventional study that influences preeclampsia, hypertensive disorders of pregnancy, or GDM.
16. Prenatal care or delivery planned at a non-network center where access to the complete electronic medical record will not be available to research staff.
17. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.

Primary outcomes:
measure: Diagnosis of Hypertensive Disorders of Pregnancy
timeFrame: Up to 14 days postpartum
Secondary outcomes:
measure: Gestational diabetes
timeFrame: As soon as possible after randomization between 14 weeks, 0 days and 21 weeks, 6 days gestation
measure: Preterm birth
timeFrame: Preterm delivery up to and less than 37 weeks gestation
measure: Cesarean Delivery
timeFrame: At the time of delivery
measure: Maternal morbidity composite
timeFrame: Within 6 weeks postpartum
measure: Maternal adverse cardiovascular outcome composite
timeFrame: By 6 weeks postpartum
measure: Fetal or Neonatal Death
timeFrame: through 72 hours postpartum
measure: Neonatal respiratory support
timeFrame: within 72 hours of delivery
measure: Birth weight
timeFrame: Immediately post birth
measure: Neonatal encephalopathy
timeFrame: within 72 hours of delivery
measure: Neonatal Seizures
timeFrame: 72 hours post birth
measure: Shoulder dystocia
timeFrame: During delivery
measure: Birth trauma
timeFrame: During delivery
measure: Intracranial hemorrhage
timeFrame: Within 72 hours post delivery
measure: Hyperbilirubinemia
timeFrame: Within 72 hours post delivery
measure: Hypoglycemia
timeFrame: Within 72 hours post delivery
measure: NICU Stay
timeFrame: Greater than or equal to 72 hours post birth
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: San Francisco
country: United States
facility: Regents of the University of California San Francisco
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve-Metro Health
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Women's Hospital of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Brown Univeristy
state: Rhode Island
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: The George Washington University Biostatistics Center
name: Rebecca Clifton, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Monica Longo, MD
role: STUDY_DIRECTOR
affiliation: Magee Women's Hospital of UPMC
name: Francesca Facco, MD
role: STUDY_CHAIR
References:
citation: Facco F. Sleep Duration, Sleep Timing, and Sleep Disordered Breathing-Associations With Obesity and Gestational Diabetes in Pregnancy. Clin Obstet Gynecol. 2021 Mar 1;64(1):196-203. doi: 10.1097/GRF.0000000000000587.