Screening and Treatment of Obstructive Sleep Apnea in High-risk Pregnancy

Screening and Treatment of Obstructive Sleep Apnea in High-risk Pregnancy: A Multi-center Randomized Controlled Trial

This is an open-label multicenter randomized-controlled trial in 3 tertiary care hospitals including Ramathibodi Hospital, Phramongkutklao Hospital and Rajavithi Hospital. The study involved screening of obstructive sleep apnea in high risk pregnancy during 1st and 2nd trimesters. Randomization to either continuous positive airway pressure (CPAP) or usual antenatal care (ANC) until delivery will be done. Efficacy of CPAP on pregnancy outcome will be analysed.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Intervention / Treatment: Device: Continuous positive airway pressure (CPAP)

Detailed Description

Screening for sleep disordered breathing (Respiratory disturbance index, RDI ≥ 5 events/hour) with type 2 sleep test will be performed in eligible subjects during early1st trimester (<16 weeks). Repeat sleep study will be done if the RDI in 1st trimester is less than 5. If the subjects meet the inclusion criteria without any of the exclusion criteria, randomization into either receiving CPAP treatment or usual ANC will be done. The pressure of CPAP machine is determined using autoCPAP machine algorithm at 90 percentile. Adjustment of CPAP machine is repeated at 24-28 week gestations. Subjects in both groups received standard usual care during ANC and outcomes were measured with similar case record forms.

• Study Type: Interventional
• Enrollment (Actual): 340
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

High risk pregnant women attending the antenatal care at the collaborated hospitals will be eligible for the study if they meet all following inclusion criteria.

Inclusion criteria (ALL criteria)

1. Singleton pregnant women age ≥ 18 years
2. Pregnant women attending the antenatal care and intending to deliver at one of the study hospitals with gestational age < 16 weeks
3. Thai nationality with ability to use Thai language proficiently both in spoken and written language.

4. Have been diagnosed as high-risk pregnancy by Obstetricians by having any of the following conditions

   1. Chronic hypertension prior to pregnancy
   2. Hypertension during pregnancy before 20 weeks gestation.
   3. Pre-eclampsia/gestational hypertension during recent pregnancy
   4. Obesity defined by pre-pregnancy body mass index (BMI) ≥ 27.5 kg/m2
   5. History of diabetes mellitus or gestational diabetes
   6. Having gestational diabetes or overt diabetes
5. Presence of snoring (either as frequent snoring ≥3 times/week or loud snoring) prior to or occurring during pregnancy OR respiratory disturbance index, RDI ≥ 5 events/hour by type 2 sleep testing at either point of testing during early pregnancy (0-16 GA week) or late pregnancy (GA 24-28week ).
6. Sign written informed consent

Exclusion Criteria:

1. Subjects' unwillingness to participate in the study at any time of the study.
2. Subject with significant medical conditions such as immunocompromised status, chronic infection (HIV infection, tuberculosis), chronic lung and cardiac conditions, chronic renal failure, thyroid disease, or neuromuscular disease.
3. Subjects with extremely severe obstructive sleep apnea (RDI ≥30) or with significant O2 desaturation <80% during sleep that might have potential benefit from the CPAP treatment.
4. Subject with known obstructive sleep apnea and currently on CPAP treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP; Nocturnal administration of continuous positive airway pressure treatment (CPAP) until delivery	Device: Continuous positive airway pressure (CPAP); A non-invasive positive pressure device that is used for the treatment of obstructive sleep apnea by splinting the collapsed upper airway during sleep
No Intervention: Control; Usual antenatal care for high risk pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of blood pressure	Difference of daytime systolic and diastolic blood pressure between 2 groups (mmHg)	During 24-28 weeks gestation
Measurement of blood pressure	Difference of daytime systolic and diastolic blood pressure between 2 groups (mmHg)	During 32-34 weeks gestation
Measurement of blood pressure	Difference of daytime mean blood pressure between 2 groups (mmHg)	During 24-28 weeks gestation
Measurement of blood pressure	Difference of daytime mean blood pressure between 2 groups(mmHg)	During 32-34 weeks gestation
Measurement of blood pressure	Difference of daytime mean blood pressure between 2 groups (mmHg)	During 18-20 weeks gestation
Measurement of blood pressure	Difference of daytime systolic and diastolic blood pressure between 2 groups (mmHg)	During 18-20 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour ambulatory blood pressure monitoring	Using non-invasive technique from pulse transit time (SomnoTouch NIBP) (mmHg)	measured twice during 24-28 week gestation, and 32-34 week gestation
24-hour ambulatory blood pressure monitoring	Using non-invasive technique from pulse transit time (SomnoTouch NIBP) (mmHg)	measured twice during 32-34 week gestation
Incidence of pregnancy induced hypertension (composite outcome1)	Incidence of hypertensive disorder of pregnancy	During pregnancy until delivery
Incidence of hypertensive disorder of pregnancy or preterm labor or fetal growth restriction or emergency Cesarean section (composite outcome2)	Incidence of hypertensive disorder of pregnancy or preterm labor or fetal growth restriction or emergency Cesarean section	During pregnancy until delivery
Incidence of preterm labor or fetal growth restriction or severe pre-eclampsia or eclampsia or death (composite outcome3)	Incidence of preterm labor or fetal growth restriction or severe pre-eclampsia or eclampsia or death	During pregnancy until delivery
Fasting plasma glucose	Fasting plasma glucose (mg/dL)	during 24-28 weeks gestation
Fasting plasma glucose	Fasting plasma glucose (mg/dL)	during 32-34 weeks gestation
Oral glucose tolerance test (OGTT)	Oral Glucose Tolerance Test (OGTT) (mg/dL)	during 24-28 weeks gestation
Fetal ultrasound results	Fetal growth (grams)	During 24-28 weeks gestation
Fetal ultrasound results	Fetal growth (grams)	During 32-34 weeks gestation
Fetal ultrasound results	Uterine Doppler arterial blood flow	During 18-20 weeks gestation
Fetal ultrasound results	Uterine Doppler arterial blood flow	During 24-28 weeks gestation
Fetal ultrasound results	Uterine Doppler arterial blood flow	During 32-34 weeks gestation
Neonatal birthweight	Neonatal birthweight (grams)	at delivery
APGAR score	The Apgar scale is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. The five criteria are summarized using words chosen to form an acronym (Appearance, Pulse, Grimace, Activity, Respiration). Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.	at 1 minute and 5 minutes after birth
Neonatal length of stay in hospital	Neonatal length of hospital stay (days) after birth until the newborn is discharged from the hospital	Through study completion up to 24 weeks
Neonatal ICU admission rate	Neonatal ICU admission rate (%) after birth	Through study completion up to 24 weeks

Collaborators and Investigators

• Sponsor: Ramathibodi Hospital
• Collaborators: National Research Council of Thailand; The Development Potentials of Thai People Project, Ramathibodi hospital
• Investigators: Principal Investigator: Visasiri Tantrakul, MD, Ramathibodi Hospital Sleep Disorder Center, Pulmonary and Care division, Department of Medicine, Ramatibodi Hospital, Mahidol University, Thailand

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2016
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (Actual): November 29, 2017

Study Record Updates

• Last Update Posted (Actual): December 7, 2021
• Last Update Submitted That Met QC Criteria: December 6, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Obstructive sleep apnea; Pre-Eclampsia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Pregnancy Complications; Hypertension; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Eclampsia; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: ID11-58-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: For the first five years after the trial is concluded (upon acceptance of the primary manuscript for publication) the data will remain accessible only to the trial investigators for the purpose of additional analyses and publications. Thereafter other interested researchers may request in writing to the Steering Committee access to the data for the purpose of meta-analyses, with approval of a protocol and signed data access agreement via contacting the principle investigators of Division of Sleep Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No