Continuous Positive Airway Pressure (CPAP) for Sleep Apnea in Pregnancy

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Trial of Continuous Positive Airway Pressure (CPAP) for Sleep Apnea in Pregnancy

Conditions
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Obstructive Sleep Apnea of Adult, Preeclampsia, Obstetrical Complications

Intervention / Treatment
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* Device: Continuous Positive Airway Pressure
* Other: Sleep Advice Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Singleton gestation. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks project gestational age. Gestational age at randomization between 14 weeks 0 days and 21 weeks 6 days based on clinical information and evaluation of the earliest ultrasound. Diagnosis with mild to moderate OSA as defined by an AHI score ≥ 5 and <30. Exclusion Criteria Previously prescribed, current or planned therapy for sleep apnea. Age < 18 years, because the rate of sleep apnea in this population is extremely low. Inability to sleep in a stable place with access to the CPAP machine at least 5 nights per week. 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. Current use of prescribed sleeping pills for insomnia. 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. Chronic renal disease with serum creatinine >1.3 mg/dL because the primary outcome would be pre-determined. Antiphospholipid antibody syndrome, because it would compromise the primary outcome diagnosis. History of medical complications such as: Active liver disease (acute hepatitis, chronic active hepatitis, persistently abnormal liver enzymes) Thrombocytopenia with platelet count <100,000 because of the difficulty in assessing the primary outcome. Active vaginal bleeding (more than spotting) at the time of randomization. Known chromosomal, genetic, major malformations or fetal demise, or planned termination of pregnancy because inclusion would compromise evaluation of secondary neonatal outcomes. Known major uterine malformations associated with adverse pregnancy outcomes. Current use of opiates (heroin, methadone, or other daily opioid use) due to inaccuracy of the home sleep test and inefficiency of CPAP. Active drug use, alcohol use, or unstable psychiatric condition. Participation in another interventional study that influences preeclampsia, hypertensive disorders of pregnancy, or GDM. 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. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous Positive Airway Pressure<br>Autotitrating CPAP with weekly contact, incentives for compliance and initial sleep advice counseling | Device: Continuous Positive Airway Pressure<br>* Autotitrating CPAP with weekly contact, incentives for compliance and initial sleep advice counseling<br>* Other names: CPAP;|
| Other: Sleep Advice Control<br>Initial sleep advice counseling alone | Other: Sleep Advice Control<br>* Initial sleep advice counseling alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of Hypertensive Disorders of Pregnancy | Subjects are considered to have the primary outcome if they meet the criteria for eclampsia, HELLP, atypical HELLP, preeclampsia, superimposed preeclampsia or antepartum gestational hypertension. | Up to 14 days postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational diabetes | Gestational diabetes by oral GTT criteria performed after randomization | As soon as possible after randomization between 14 weeks, 0 days and 21 weeks, 6 days gestation | 
| Preterm birth | Preterm birth less than 34 weeks and less than 37 weeks | Preterm delivery up to and less than 37 weeks gestation | 
| Cesarean Delivery | Delivery by cesarean section | At the time of delivery | 
| Maternal morbidity composite | Maternal morbidity composite defined as the occurrence of one of the following: Maternal death Transfusion of ≥ 4 units of PRBC within 6 weeks postpartum ICU admission within 6 weeks postpartum | Within 6 weeks postpartum | 
| Maternal adverse cardiovascular outcome composite | Maternal adverse cardiovascular outcome composite defined as the occurrence of one or more of the following: Venous thromboembolism New onset heart failure with ejection fraction (EF) < 40% Cerebrovascular accident Myocardial infarction New onset atrial fibrillation | By 6 weeks postpartum | 
| Fetal or Neonatal Death | Antepartum, intrapartum, or neonatal death | through 72 hours postpartum | 
| Neonatal respiratory support | Intubation, continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) for ventilation or cardiopulmonary resuscitation | within 72 hours of delivery | 
| Birth weight | Small for gestational age defined as < 5th percentile weight for gestational age, assessed specifically by sex and race of the infant based on United States birth certificate data Large for gestational age defined as greater than the 90th percentile for gestational age. Macrosomia defined as birthweight > 4000 grams | Immediately post birth | 
| Neonatal encephalopathy | Neonatal encephalopathy as defined by the NICHD Neonatal Research Network criteria | within 72 hours of delivery | 
| Neonatal Seizures | Neonatal seizure activity confirmed by central review | 72 hours post birth | 
| Shoulder dystocia | Shoulder dystocia during delivery | During delivery | 
| Birth trauma | Bone fractures, brachial plexus palsy, other neurologic injury, retinal hemorrhage, or facial nerve palsy | During delivery | 
| Intracranial hemorrhage | Intraventricular hemorrhage grades III and IV, subgaleal hematoma, subdural hematoma, or subarachnoid hematoma | Within 72 hours post delivery | 
| Hyperbilirubinemia | Hyperbilirubinemia requiring phototherapy or exchange transfusion | Within 72 hours post delivery | 
| Hypoglycemia | glucose < 35 mg/dl requiring IV therapy | Within 72 hours post delivery | 
| NICU Stay | Neonatal Intensive Care Unit stay | Greater than or equal to 72 hours post birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CPAP, Apnea, pregnancy