Aspirin Resistance in OSA Patients

Obstructive Sleep Apnea Clinical Trial

Official title:

Aspirin Resistance in Obstructive Sleep Apnea Patients (ARISA Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03930875
• Other study ID #: 17-08-229-337
• Status: Completed
• Start date: December 12, 2017
• Est. completion date: September 7, 2018

Study information

• Verified date: April 2019
• Source: Danbury Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Obstructive Sleep Apnea (OSA) patients are at increased risk of major cardiovascular events, so many patients take aspirin for prevention. Poor responsiveness to aspirin is a major clinical concern because it can potentially worsen the prognosis of OSA patients. However, continuous positive airway pressure (CPAP) therapy that is considered standard of care for OSA treatment may potentially lead to improvement in responsiveness to aspirin. This study will determine whether CPAP therapy decreases patients' aspirin resistance in OSA patients with a new diagnosis or existing moderate to severe OSA who are treated with CPAP and take aspirin for prevention.

Description:

Obstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder that afflicts more than 25 million adults in the United States. This number continues to rise yearly due to increased incidence of obesity in the United States. The prevalence of OSA among males and females is also on the rise with 34% of males and 17% of females diagnosed with this disease.

OSA is characterized as intermittent pharyngeal soft-tissue obstruction due to anatomical or positional etiology during sleep. This leads to episodes of hypoxemia and apneas which result in overall sleep fragmentation. The pathophysiology associated with OSA is complex. However, some proposed causes of OSA include hypoxia during sleep which causes increased circulating catecholamines and sympathetic activation, free radical formation leading to oxidative stress, increased cytokine release and endothelial dysfunction. These proposed mechanisms are also associated with increased platelet aggregation and hyperactivity and increase a patient's overall risk for cardiovascular morbidities.

Many patients with cardiovascular co-morbidities are taking aspirin for primary or secondary prevention. With a concomitant diagnosis of OSA, it is thought that these patients who are taking aspirin on a daily basis may become resistant to its effects based on how their OSA is controlled (ie. CPAP vs. Non-CPAP). Although aspirin resistance has been noted to be a "laboratory phenomenon," there have been studies which have shown a three-fold increase in cardiovascularco- morbidities in patients who were found to be aspirin resistant. In this study, it is our goal to determine the prevalence of aspirin resistance in patients who have a diagnosis of OSA and undergoing treatment with CPAP or Non-CPAP methods by measuring Aspirin Resistant Units (ARUs) using light aggregometry. It is our overall objective to determine whether or not OSA is an independent risk factor for aspirin resistance.

OSA patients are at increased risk of major cardiovascular events and aspirin resistance is associated with poor cardiovascular outcomes. Studying aspirin responsiveness in OSA patients may help to elucidate the potential role of platelet function testing, including the possible clinical implications of an aspirin therapy regimen guided by platelet function testing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: September 7, 2018
• Est. primary completion date: September 7, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria for Control Group:

• No OSA (based on home or attended polysomnography) determined by negative sleep study (HSAT or NPSG) REI/AHI < 5 (if a home study was done and found negative or equivocal an attended study is required to rule out sleep apnea)

• Patient is taking aspirin at a dose of 81 mg/day for at least a week last dose taken within 24 hours prior to enrollment.

Inclusion Criteria for "CPAP-Naïve" Cohort:

• Diagnosis of OSA (based on home or attended sleep study) with an REI/AHI = 15 with or without symptoms or REI/AHI = 5 with symptoms of sleep apnea in a patient 18-85 years old.

• Patient is taking aspirin at a dose of 81mg/day for at least a week, last dose taken within 24 hours prior to enrollment.

Inclusion Criteria for "CPAP-treated" Cohort:

• Diagnosis of OSA (based on home or attended sleep study) with an REI/AHI = 15 with or without symptoms or REI/AHI = 5 with symptoms of sleep apnea in a patient 18-85 years old.

• CPAP has been started within the last 2 years

• Patient is taking aspirin at a dose of 81mg/day for at least a week, last dose taken within 24 hours prior to enrollment.

Exclusion Criteria for all cohorts including control group:

• Patient is not able to provide informed consent

• Patient has taken at least one dose of a non-aspirin NSAID within the last 3 days

• Patient has taken at least one dose of another (non-aspirin) anti-platelet agent(s) (clopidogrel, abciximab, eptifibatide, tirofiban, cilostazol, dipyridamole, prasugrel, ticlopidine, ticagrelor) in the last 7 days.

• Patient has taken at least one dose of vitamin K antagonist (warfarin) in the last 7 days or heparin (low molecular weight or unfractionated) in the last 24 hours

• Patient has taken steroids (intravenous, oral, or topical) within the last 2 weeks

• Signs and symptoms of an active infection:

• Temperature = 100.4

• Productive cough

• Rhinorrhea

• Dysuria

• Diarrhea

• Signs and symptoms of a local inflammatory reaction

• Pain

• Warmth

• Erythema

• Swelling

• Any history of a systemic inflammatory disorder

• Any history of diabetes mellitus if no HbA1C measurement obtained within 6 months is available; if HbA1C measurement obtained within 6 months is available, patient will be included.

• Any history of chronic kidney disease

• Pregnant women, and women in labor

Related Conditions & MeSH terms

• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Other:
• Aspirin Resistance testing
Aspirin resistance will be measured using platelet aggregometry (VerifyNow assay)

Locations

Country	Name	City	State
United States	Danbury Hospital	Danbury	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Danbury Hospital	Accriva Diagnostics

Country where clinical trial is conducted

United States, 

References & Publications (21)

Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, Martínez-Alonso M, Carmona C, Barceló A, Chiner E, Masa JF, Gonzalez M, Marín JM, Garcia-Rio F, Diaz de Atauri J, Terán J, Mayos M, de la Peña M, Monasterio C, del Campo F, Montserrat JM; Spanish Sleep And Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012 May 23;307(20):2161-8. doi: 10.1001/jama.2012.4366. — View Citation

Buchner NJ, Sanner BM, Borgel J, Rump LC. Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1274-80. Epub 2007 Aug 2. — View Citation

Cai G, Zhou W, Lu Y, Chen P, Lu Z, Fu Y. Aspirin resistance and other aspirin-related concerns. Neurol Sci. 2016 Feb;37(2):181-9. doi: 10.1007/s10072-015-2412-x. Epub 2015 Nov 14. Review. — View Citation

Cheng G, Shan J, Xu G, Liu P, Zhou Y, Zhu Y, Lu X. Relationship between endothelial dysfunction, oxidant stress and aspirin resistance in patients with stable coronary heart disease. J Clin Pharm Ther. 2007 Jun;32(3):287-92. — View Citation

Grinstein J, Cannon CP. Aspirin resistance: current status and role of tailored therapy. Clin Cardiol. 2012 Nov;35(11):673-81. doi: 10.1002/clc.22031. Epub 2012 Jun 27. Review. — View Citation

Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003 Mar 19;41(6):961-5. Erratum in: J Am Coll Cardiol. 2006 Nov 7;48(9):1918. — View Citation

Hopps E, Caimi G. Obstructive Sleep Apnea Syndrome: Links Betwen Pathophysiology and Cardiovascular Complications. Clin Invest Med. 2015 Dec 4;38(6):E362-70. Review. — View Citation

Jordan AS, McSharry DG, Malhotra A. Adult obstructive sleep apnoea. Lancet. 2014 Feb 22;383(9918):736-47. doi: 10.1016/S0140-6736(13)60734-5. Epub 2013 Aug 2. Review. — View Citation

Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008 Jan 26;336(7637):195-8. doi: 10.1136/bmj.39430.529549.BE. Epub 2008 Jan 17. Review. — View Citation

Kuliczkowski W, Witkowski A, Polonski L, Watala C, Filipiak K, Budaj A, Golanski J, Sitkiewicz D, Pregowski J, Gorski J, Zembala M, Opolski G, Huber K, Arnesen H, Kristensen SD, De Caterina R. Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J. 2009 Feb;30(4):426-35. doi: 10.1093/eurheartj/ehn562. Epub 2009 Jan 27. Review. — View Citation

Lee PY, Chen WH, Ng W, Cheng X, Kwok JY, Tse HF, Lau CP. Low-dose aspirin increases aspirin resistance in patients with coronary artery disease. Am J Med. 2005 Jul;118(7):723-7. — View Citation

Maeder MT, Schoch OD, Rickli H. A clinical approach to obstructive sleep apnea as a risk factor for cardiovascular disease. Vasc Health Risk Manag. 2016 Mar 21;12:85-103. doi: 10.2147/VHRM.S74703. eCollection 2016. Review. — View Citation

Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005 Mar 19-25;365(9464):1046-53. — View Citation

Oga T, Chin K, Tabuchi A, Kawato M, Morimoto T, Takahashi K, Handa T, Takahashi K, Taniguchi R, Kondo H, Mishima M, Kita T, Horiuchi H. Effects of obstructive sleep apnea with intermittent hypoxia on platelet aggregability. J Atheroscler Thromb. 2009;16(6):862-9. Epub 2009 Dec 22. — View Citation

Ozben S, Ozben B, Tanrikulu AM, Ozer F, Ozben T. Aspirin resistance in patients with acute ischemic stroke. J Neurol. 2011 Nov;258(11):1979-86. doi: 10.1007/s00415-011-6052-7. Epub 2011 Apr 21. — View Citation

Pasala T, Hoo JS, Lockhart MK, Waheed R, Sengodan P, Alexander J, Gandhi S. Aspirin Resistance Predicts Adverse Cardiovascular Events in Patients with Symptomatic Peripheral Artery Disease. Tex Heart Inst J. 2016 Dec 1;43(6):482-487. doi: 10.14503/THIJ-14-4986. eCollection 2016 Dec. — View 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. — View Citation

Schwammenthal Y, Tsabari R, Shenkman B, Schwartz R, Matetzky S, Lubetsky A, Orion D, Israeli-Korn S, Chapman J, Savion N, Varon D, Tanne D. Aspirin responsiveness in acute brain ischaemia: association with stroke severity and clinical outcome. Cerebrovasc Dis. 2008;25(4):355-61. doi: 10.1159/000118382. Epub 2008 Feb 28. — View Citation

Sökücü SN, Ozdemir C, Dalar L, Karasulu L, Aydin S, Altin S. Complete blood count alterations after six months of continuous positive airway pressure treatment in patients with severe obstructive sleep apnea. J Clin Sleep Med. 2014 Aug 15;10(8):873-8. doi: 10.5664/jcsm.3958. — View Citation

Tazbirek M, Slowinska L, Kawalski M, Pierzchala W. The rheological properties of blood and the risk of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS). Folia Histochem Cytobiol. 2011;49(2):206-10. Review. — View Citation

Varol E, Ozturk O, Yucel H, Gonca T, Has M, Dogan A, Akkaya A. The effects of continuous positive airway pressure therapy on mean platelet volume in patients with obstructive sleep apnea. Platelets. 2011;22(7):552-6. doi: 10.3109/09537104.2011.578182. Epub 2011 May 19. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The prevalence of aspirin resistance in patients with newly diagnosed OSA taking aspirin for primary or secondary prevention.	The prevalence of aspirin resistance, measured by platelet aggregometry, in patients with newly diagnosed OSA who take aspirin for primary or secondary prevention.	Immediately after consent is obtained (baseline)
Secondary	The prevalence of aspirin resistance in OSA patients who take aspirin for primary or secondary prevention and are currently being treated with CPAP.	The prevalence of aspirin resistance in those patients with OSA on aspirin for primary or secondary prevention who are currently being treated with CPAP.	Immediately after consent is obtained (baseline)