Clinical trial NCT02755831: Targeted CPAP Therapy for Obstructive Sleep Apnea in Pregnancy
Official title: Randomized Controlled Trial for a Sleep Study and Targeted CPAP Therapy for Obstructive Sleep Apnea to Reduce the Incidence Adverse Pregnancy Related Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea
Keywords: OSA
pregnancy
adverse pregnancy outcomes
continuous positive airway pressure
preeclampsia
gestational diabetes
Lead sponsor: United States Naval Medical Center, San Diego
Sponsor class: FED
First posted: 2016-04-29
Enrollment: 193
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Prospective, randomized controlled trial. Pregnant women in early pregnancy will be randomized to either the Sleep Study + CPAP (Continuous Positive Airway Pressure Therapy) group or to a Standard Prenatal Care group. Subjects in the Sleep Study + CPAP group will complete a sleep study (WatchPAT-200, Itamar Medical, Inc.) and have CPAP initiated if the Apnea Hypopnea Index (AHI) ≥5 as indicated, in early and late pregnancy, whereas the other group will receive standard prenatal care. All subjects will complete a sleep study again between 8 to 12 weeks postpartum.

Detailed description: Objective/Hypothesis: The purpose of this study is to determine if parturients identified as high risk for obstructive sleep apnea (OSA; defined as an apnea hypopnea index \[AHI\] ≥5 events/hour) who are randomized to receive an unattended sleep study during early and late pregnancy (early = between 6 and 16 weeks; late = between 27 and 33 weeks) plus initiation of CPAP therapy if the AHI ≥5 events/hour and standard prenatal care have a decreased incidence of adverse pregnancy outcomes (defined as a composite variable which includes gestational hypertension, preeclampsia, eclampsia, gestational diabetes, preterm birth, low birth weight, or stillbirth) at the time of delivery when compared to a group who receives standard prenatal care only (no sleep study and CPAP initiation). At 8 to 12 months postpartum subjects in both groups will complete a sleep study.

Eligibility criteria: Inclusion Criteria

1. At least one of the following risk factors for OSA: prepregnancy BMI ≥ 30kg/m2, chronic hypertension, pregestational diabetes, twin gestation, or a history of prior pregnancy affected by: preeclampsia, eclampsia or fetal growth restriction.
2. Between 6 and 16 weeks gestation at time of enrollment.

Exclusion Criteria

1. Current diagnosis and treatment of OSA.
2. Patient refusal to randomization.
3. Permanent Pacemaker (interfere with WATCHPAT sleep study).
4. Currently taking alpha blockers or nitrates (interfere with WATCHPAT sleep study).
5. Coronary artery disease or congestive heart failure or cardiomyopathy.
6. Not delivering and completing their postpartum visit at Naval Medical Center San Diego (NMCSD).
7. Inability to read or understand the consent.
8. \<18 years of age.

Primary outcomes:
measure: Number of Participants With Adverse Pregnancy Outcomes
timeFrame: time of delivery
Secondary outcomes:
measure: Incidence of Obstructive Sleep Apnea (OSA) in Early Pregnancy - Treatment Group Only (6-16 Weeks)
timeFrame: early pregnancy (6-16 weeks)
measure: Incidence of OSA in Late Pregnancy- Treatment Group Only (27-33 Weeks)
timeFrame: 27-33 weeks
measure: Incidence of OSA at 8 to 12 Weeks Postpartum in Treatment and Control Group
timeFrame: 8-12 weeks postpartum
measure: Hospital Costs at Time of Delivery
timeFrame: Hospital costs at time of delivery
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Naval Medical Center
state: California
Study officials:
affiliation: United States Naval Medical Center, San Diego
name: Dennis L Spence, PhD
role: STUDY_DIRECTOR
References:
citation: Poyares D, Guilleminault C, Hachul H, Fujita L, Takaoka S, Tufik S, Sass N. Pre-eclampsia and nasal CPAP: part 2. Hypertension during pregnancy, chronic snoring, and early nasal CPAP intervention. Sleep Med. 2007 Dec;9(1):15-21. doi: 10.1016/j.sleep.2007.04.019. Epub 2007 Jul 20.
citation: Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D'Agostino RB, Newman AB, Lebowitz MD, Pickering TG. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000 Apr 12;283(14):1829-36. doi: 10.1001/jama.283.14.1829.
citation: Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, Stubbs R, Hla KM. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008 Aug;31(8):1071-8.
citation: Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009 Aug;108(5):246-9.
citation: Memtsoudis SG, Sun X, Chiu YL, Nurok M, Stundner O, Pastores SM, Mazumdar M. Utilization of critical care services among patients undergoing total hip and knee arthroplasty: epidemiology and risk factors. Anesthesiology. 2012 Jul;117(1):107-16. doi: 10.1097/ALN.0b013e31825afd36.
citation: Luque-Fernandez MA, Bain PA, Gelaye B, Redline S, Williams MA. Sleep-disordered breathing and gestational diabetes mellitus: a meta-analysis of 9,795 participants enrolled in epidemiological observational studies. Diabetes Care. 2013 Oct;36(10):3353-60. doi: 10.2337/dc13-0778.
citation: Ding XX, Wu YL, Xu SJ, Zhang SF, Jia XM, Zhu RP, Hao JH, Tao FB. A systematic review and quantitative assessment of sleep-disordered breathing during pregnancy and perinatal outcomes. Sleep Breath. 2014 Dec;18(4):703-13. doi: 10.1007/s11325-014-0946-4. Epub 2014 Feb 12.
citation: Pamidi S, Pinto LM, Marc I, Benedetti A, Schwartzman K, Kimoff RJ. Maternal sleep-disordered breathing and adverse pregnancy outcomes: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014 Jan;210(1):52.e1-52.e14. doi: 10.1016/j.ajog.2013.07.033. Epub 2013 Aug 2.
citation: Louis J, Auckley D, Miladinovic B, Shepherd A, Mencin P, Kumar D, Mercer B, Redline S. Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women. Obstet Gynecol. 2012 Nov;120(5):1085-92. doi: 10.1097/AOG.0b013e31826eb9d8.
citation: American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):268-86. doi: 10.1097/ALN.0000000000000053. No abstract available.
citation: Ankichetty SP, Angle P, Joselyn AS, Chinnappa V, Halpern S. Anesthetic considerations of parturients with obesity and obstructive sleep apnea. J Anaesthesiol Clin Pharmacol. 2012 Oct;28(4):436-43. doi: 10.4103/0970-9185.101895.
citation: Reutrakul S, Zaidi N, Wroblewski K, Kay HH, Ismail M, Ehrmann DA, Van Cauter E. Interactions between pregnancy, obstructive sleep apnea, and gestational diabetes mellitus. J Clin Endocrinol Metab. 2013 Oct;98(10):4195-202. doi: 10.1210/jc.2013-2348. Epub 2013 Aug 21.
citation: Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein MD; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009 Jun 15;5(3):263-76.
citation: Louis JM, Mogos MF, Salemi JL, Redline S, Salihu HM. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009. Sleep. 2014 May 1;37(5):843-9. doi: 10.5665/sleep.3644.
citation: Facco FL, Ouyang DW, Zee PC, Grobman WA. Sleep disordered breathing in a high-risk cohort prevalence and severity across pregnancy. Am J Perinatol. 2014 Nov;31(10):899-904. doi: 10.1055/s-0033-1363768. Epub 2014 Feb 10.
citation: Pien GW, Pack AI, Jackson N, Maislin G, Macones GA, Schwab RJ. Risk factors for sleep-disordered breathing in pregnancy. Thorax. 2014 Apr;69(4):371-7. doi: 10.1136/thoraxjnl-2012-202718. Epub 2013 Nov 21.
citation: Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013 May 1;177(9):1006-14. doi: 10.1093/aje/kws342. Epub 2013 Apr 14.
citation: Morgenthaler TI, Aurora RN, Brown T, Zak R, Alessi C, Boehlecke B, Chesson AL Jr, Friedman L, Kapur V, Maganti R, Owens J, Pancer J, Swick TJ; Standards of Practice Committee of the AASM; American Academy of Sleep Medicine. Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep. 2008 Jan;31(1):141-7. doi: 10.1093/sleep/31.1.141.
citation: Guilleminault C, Palombini L, Poyares D, Takaoka S, Huynh NT, El-Sayed Y. Pre-eclampsia and nasal CPAP: part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: preliminary findings. Sleep Med. 2007 Dec;9(1):9-14. doi: 10.1016/j.sleep.2007.04.020. Epub 2007 Jul 17.
citation: Whitehead C, Tong S, Wilson D, Howard M, Walker SP. Treatment of early-onset preeclampsia with continuous positive airway pressure. Obstet Gynecol. 2015 May;125(5):1106-1109. doi: 10.1097/AOG.0000000000000508.
citation: Facco F. Sleep-disordered breathing in pregnancy: a brief summary of current knowledge. BJOG. 2014 Dec;121(13):1694. doi: 10.1111/1471-0528.12888. Epub 2014 May 30. No abstract available.
citation: Izci-Balserak B, Pien GW. Sleep-disordered breathing and pregnancy: potential mechanisms and evidence for maternal and fetal morbidity. Curr Opin Pulm Med. 2010 Nov;16(6):574-82. doi: 10.1097/MCP.0b013e32833f0d55.
citation: Volna J, Kemlink D, Kalousova M, Vavrova J, Majerova V, Mestek O, Svarcova J, Sonka K, Zima T. Biochemical oxidative stress-related markers in patients with obstructive sleep apnea. Med Sci Monit. 2011 Sep;17(9):CR491-7. doi: 10.12659/msm.881935.
citation: Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension. 2013 Dec;62(6):1046-54. doi: 10.1161/HYPERTENSIONAHA.113.01892. Epub 2013 Sep 23.
citation: Fung AM, Wilson DL, Lappas M, Howard M, Barnes M, O'Donoghue F, Tong S, Esdale H, Fleming G, Walker SP. Effects of maternal obstructive sleep apnoea on fetal growth: a prospective cohort study. PLoS One. 2013 Jul 24;8(7):e68057. doi: 10.1371/journal.pone.0068057. Print 2013.
citation: Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997 Sep;20(9):705-6. doi: 10.1093/sleep/20.9.705.
citation: Reid J, Glew RA, Skomro R, Fenton M, Cotton D, Olatunbosun F, Gjevre J, Guilleminault C. Sleep disordered breathing and gestational hypertension: postpartum follow-up study. Sleep. 2013 May 1;36(5):717-721B. doi: 10.5665/sleep.2634.
citation: Hermes W, Tamsma JT, Grootendorst DC, Franx A, van der Post J, van Pampus MG, Bloemenkamp KW, Porath M, Mol BW, de Groot CJ. Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study. BMC Pregnancy Childbirth. 2013 Jun 4;13:126. doi: 10.1186/1471-2393-13-126.
citation: Chen YH, Kang JH, Lin CC, Wang IT, Keller JJ, Lin HC. Obstructive sleep apnea and the risk of adverse pregnancy outcomes. Am J Obstet Gynecol. 2012 Feb;206(2):136.e1-5. doi: 10.1016/j.ajog.2011.09.006. Epub 2011 Sep 16.
citation: Facco FL, Ouyang DW, Zee PC, Grobman WA. Development of a pregnancy-specific screening tool for sleep apnea. J Clin Sleep Med. 2012 Aug 15;8(4):389-94. doi: 10.5664/jcsm.2030.
citation: Hedner J, Pillar G, Pittman SD, Zou D, Grote L, White DP. A novel adaptive wrist actigraphy algorithm for sleep-wake assessment in sleep apnea patients. Sleep. 2004 Dec 15;27(8):1560-6. doi: 10.1093/sleep/27.8.1560.
citation: Penzel T, Kesper K, Pinnow I, Becker HF, Vogelmeier C. Peripheral arterial tonometry, oximetry and actigraphy for ambulatory recording of sleep apnea. Physiol Meas. 2004 Aug;25(4):1025-36. doi: 10.1088/0967-3334/25/4/019.
citation: Ahmadi N, Chung SA, Gibbs A, Shapiro CM. The Berlin questionnaire for sleep apnea in a sleep clinic population: relationship to polysomnographic measurement of respiratory disturbance. Sleep Breath. 2008 Mar;12(1):39-45. doi: 10.1007/s11325-007-0125-y.
citation: Chung F, Yegneswaran B, Liao P, Chung SA, Vairavanathan S, Islam S, Khajehdehi A, Shapiro CM. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008 May;108(5):812-21. doi: 10.1097/ALN.0b013e31816d83e4.
citation: Rogers AE, Caruso CC, Aldrich MS. Reliability of sleep diaries for assessment of sleep/wake patterns. Nurs Res. 1993 Nov-Dec;42(6):368-72.
citation: Haythornthwaite JA, Hegel MT, Kerns RD. Development of a sleep diary for chronic pain patients. J Pain Symptom Manage. 1991 Feb;6(2):65-72. doi: 10.1016/0885-3924(91)90520-e.
citation: Finkel KJ, Searleman AC, Tymkew H, Tanaka CY, Saager L, Safer-Zadeh E, Bottros M, Selvidge JA, Jacobsohn E, Pulley D, Duntley S, Becker C, Avidan MS. Prevalence of undiagnosed obstructive sleep apnea among adult surgical patients in an academic medical center. Sleep Med. 2009 Aug;10(7):753-8. doi: 10.1016/j.sleep.2008.08.007. Epub 2009 Jan 30.
citation: Kalkhoff SM, Lutgendorf MA, Morrison TC, Han T, Spence DL. A randomized controlled trial of sleep study surveillance with targeted autoregulated positive airway pressure therapy for obstructive sleep apnea in pregnancy. Am J Obstet Gynecol MFM. 2022 May;4(3):100571. doi: 10.1016/j.ajogmf.2022.100571. Epub 2022 Jan 17.