drugset / Trial / NCT02409680
Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)
Completed
11976 enrolled
NICHD Global Network for Women's and Children's Health
Jawaharlal Nehru Medical College · collabThomas Jefferson University · collab
RandomizedParallel-groupDouble-blindTreatment
Summary
Available data suggest that low dose aspirin may be a safe, widely available and inexpensive intervention that may significantly reduce the risk of preterm birth. However, this possibility needs to be proven in a properly designed randomized controlled trial (RCT) with preterm birth as the primary outcome. Such a clinical trial in a racially, ethnically and geographically diverse population could best be accomplished by the established infrastructure of the Global Network for Women's and Children's Health Research (GN).
Timeline
- Start
- 2016-03-23
- Primary completion
- 2019-04-11
- Completion
- 2019-04-11
Publications
- Background Abramovici A, Cantu J, Jenkins SM. Tocolytic therapy for acute preterm labor. Obstet Gynecol Clin North Am. 2012 Mar;39(1):77-87. doi: 10.1016/j.ogc.2011.12.003. Epub 2012 Jan 4.
- Background Ananth CV, Joseph KS, Oyelese Y, Demissie K, Vintzileos AM. Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000. Obstet Gynecol. 2005 May;105(5 Pt 1):1084-91. doi: 10.1097/01.AOG.0000158124.96300.c7.
- Background Anderson RN, Smith BL. Deaths: leading causes for 2001. Natl Vital Stat Rep. 2003 Nov 7;52(9):1-85.
- Background Baschat AA, Guclu S, Kush ML, Gembruch U, Weiner CP, Harman CR. Venous Doppler in the prediction of acid-base status of growth-restricted fetuses with elevated placental blood flow resistance. Am J Obstet Gynecol. 2004 Jul;191(1):277-84. doi: 10.1016/j.ajog.2003.11.028.
- Background Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010 Jan;88(1):31-8. doi: 10.2471/BLT.08.062554. Epub 2009 Sep 25.
- Background Becker DM, Segal J, Vaidya D, Yanek LR, Herrera-Galeano JE, Bray PF, Moy TF, Becker LC, Faraday N. Sex differences in platelet reactivity and response to low-dose aspirin therapy. JAMA. 2006 Mar 22;295(12):1420-7. doi: 10.1001/jama.295.12.1420.
- Background Bower SJ, Harrington KF, Schuchter K, McGirr C, Campbell S. Prediction of pre-eclampsia by abnormal uterine Doppler ultrasound and modification by aspirin. Br J Obstet Gynaecol. 1996 Jul;103(7):625-9. doi: 10.1111/j.1471-0528.1996.tb09829.x.
- Background CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7;349(9066):1641-9.
- Background Chavarria ME, Lara-Gonzalez L, Gonzalez-Gleason A, Garcia-Paleta Y, Vital-Reyes VS, Reyes A. Prostacyclin/thromboxane early changes in pregnancies that are complicated by preeclampsia. Am J Obstet Gynecol. 2003 Apr;188(4):986-92. doi: 10.1067/mob.2003.203.
- Background Chien PF, Arnott N, Gordon A, Owen P, Khan KS. How useful is uterine artery Doppler flow velocimetry in the prediction of pre-eclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG. 2000 Feb;107(2):196-208. doi: 10.1111/j.1471-0528.2000.tb11690.x.
- Background CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. Lancet. 1994 Mar 12;343(8898):619-29.
- Background ACOG committee opinion no. 561: Nonmedically indicated early-term deliveries. Obstet Gynecol. 2013 Apr;121(4):911-915. doi: 10.1097/01.AOG.0000428649.57622.a7.
- Background Coomarasamy A, Braunholtz D, Song F, Taylor R, Khan KS. Individualising use of aspirin to prevent pre-eclampsia: a framework for clinical decision making. BJOG. 2003 Oct;110(10):882-8. No abstract available.
- Background Coomarasamy A, Honest H, Papaioannou S, Gee H, Khan KS. Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review. Obstet Gynecol. 2003 Jun;101(6):1319-32. doi: 10.1016/s0029-7844(03)00169-8.
- Background Duley L, Henderson-Smart DJ, Knight M, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2004;(1):CD004659. doi: 10.1002/14651858.CD004659.
- Background Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659. doi: 10.1002/14651858.CD004659.pub2.
- Background Ebrashy A, Ibrahim M, Marzook A, Yousef D. Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14-16 weeks pregnancy: randomized controlled clinical trial. Croat Med J. 2005 Oct;46(5):826-31.
- Background Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum. 2001 Jun;44(6):1466-7. doi: 10.1002/1529-0131(200106)44:63.0.CO;2-C. No abstract available.
- Background FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts LJ 2nd, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983 Mar;71(3):676-88. doi: 10.1172/jci110814.
- Background Goffinet F, Aboulker D, Paris-Llado J, Bucourt M, Uzan M, Papiernik E, Breart G. Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results: a multicenter randomised controlled trial. BJOG. 2001 May;108(5):510-8. doi: 10.1111/j.1471-0528.2001.00116.x.
- Background Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. doi: 10.1016/S0140-6736(08)60074-4.
- Background Goldenberg RL, Rouse DJ. Prevention of premature birth. N Engl J Med. 1998 Jul 30;339(5):313-20. doi: 10.1056/NEJM199807303390506. No abstract available.
- Background Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2012. Natl Vital Stat Rep. 2013 Sep;62(3):1-20.
- Background Heyborne KD. Preeclampsia prevention: lessons from the low-dose aspirin therapy trials. Am J Obstet Gynecol. 2000 Sep;183(3):523-8. doi: 10.1067/mob.2000.106757.
- Background Kajantie E, Eriksson JG, Osmond C, Thornburg K, Barker DJ. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke. 2009 Apr;40(4):1176-80. doi: 10.1161/STROKEAHA.108.538025. Epub 2009 Mar 5.
- Background Kim YJ, Lee BE, Park HS, Kang JG, Kim JO, Ha EH. Risk factors for preterm birth in Korea: a multicenter prospective study. Gynecol Obstet Invest. 2005;60(4):206-12. doi: 10.1159/000087207. Epub 2005 Jul 26.
- Background Knight M, Duley L, Henderson-Smart DJ, King JF. Antiplatelet agents for preventing and treating pre-eclampsia. Cochrane Database Syst Rev. 2000;(2):CD000492. doi: 10.1002/14651858.CD000492.
- Background Kozer E, Nikfar S, Costei A, Boskovic R, Nulman I, Koren G. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis. Am J Obstet Gynecol. 2002 Dec;187(6):1623-30. doi: 10.1067/mob.2002.127376.
- Background Landau D, Shelef I, Polacheck H, Marks K, Holcberg G. Perinatal vasoconstrictive renal insufficiency associated with maternal nimesulide use. Am J Perinatol. 1999;16(9):441-4. doi: 10.1055/s-1999-6810.
- Background Landolfi R, Cipriani MC, Novarese L. Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: pathogenetic mechanisms and prevention. Best Pract Res Clin Haematol. 2006;19(3):617-33. doi: 10.1016/j.beha.2005.07.011.
- Background Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ. 2003 Aug 16;327(7411):368. doi: 10.1136/bmj.327.7411.368.
- Background Loe SM, Sanchez-Ramos L, Kaunitz AM. Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis. Obstet Gynecol. 2005 Jul;106(1):173-9. doi: 10.1097/01.AOG.0000168622.56478.df.
- Background Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy-induced hypertension. Italian study of aspirin in pregnancy. Lancet. 1993 Feb 13;341(8842):396-400.
- Background March of Dimes, Save the Children, WHO. (2012). Born Too Soon: The Global Action Report on Preterm Birth. (M. V. K. CP Howson JE Lawn., Ed.). Geneva: World Health Organization.
- Background Marret S, Marchand L, Kaminski M, Larroque B, Arnaud C, Truffert P, Thirez G, Fresson J, Roze JC, Ancel PY; EPIPAGE Study Group. Prenatal low-dose aspirin and neurobehavioral outcomes of children born very preterm. Pediatrics. 2010 Jan;125(1):e29-34. doi: 10.1542/peds.2009-0994. Epub 2009 Dec 21.
- Background Mathews TJ, Menacker F, MacDorman MF; Centers for Disease Control and Prevention, National Center for Health Statistics. Infant mortality statistics from the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep. 2004 Nov 24;53(10):1-29.
- Background McCormick MC, Richardson DK. Premature infants grow up. N Engl J Med. 2002 Jan 17;346(3):197-8. doi: 10.1056/NEJM200201173460310. No abstract available.
- Background Morris JM, Fay RA, Ellwood DA, Cook CM, Devonald KJ. A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow. Obstet Gynecol. 1996 Jan;87(1):74-8. doi: 10.1016/0029-7844(95)00340-1.
- Background Newnham JP, Godfrey M, Walters BJ, Phillips J, Evans SF. Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. Aust N Z J Obstet Gynaecol. 1995 Nov;35(4):370-4. doi: 10.1111/j.1479-828x.1995.tb02144.x.
- Background Norgard B, Puho E, Czeizel AE, Skriver MV, Sorensen HT. Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. Am J Obstet Gynecol. 2005 Mar;192(3):922-3. doi: 10.1016/j.ajog.2004.10.598.
- Background Norton ME, Merrill J, Cooper BA, Kuller JA, Clyman RI. Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med. 1993 Nov 25;329(22):1602-7. doi: 10.1056/NEJM199311253292202.
- Background Papageorghiou AT, Yu CK, Erasmus IE, Cuckle HS, Nicolaides KH. Assessment of risk for the development of pre-eclampsia by maternal characteristics and uterine artery Doppler. BJOG. 2005 Jun;112(6):703-9. doi: 10.1111/j.1471-0528.2005.00519.x.
- Background Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005 Dec 1;353(22):2373-83. doi: 10.1056/NEJMra052717. No abstract available.
- Background Peruzzi L, Gianoglio B, Porcellini MG, Coppo R. Neonatal end-stage renal failure associated with maternal ingestion of cyclo-oxygenase-type-1 selective inhibitor nimesulide as tocolytic. Lancet. 1999 Nov 6;354(9190):1615. doi: 10.1016/S0140-6736(99)03105-0.
- Background Physicians' health study: aspirin and primary prevention of coronary heart disease. N Engl J Med. 1989 Dec 28;321(26):1825-8. doi: 10.1056/NEJM198912283212610. No abstract available.
- Background RE, B., & AS, B. (2006). Preterm Birth: Causes, Consequences, and Prevention. (I. of M. of the Academies, Ed.). Washington, DC: The National Academies Press.
- Background Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31;352(13):1293-304. doi: 10.1056/NEJMoa050613. Epub 2005 Mar 7.
- Background Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008 Jan 19;371(9608):261-9. doi: 10.1016/S0140-6736(08)60136-1.
- Background Schisterman EF, Silver RM, Lesher LL, Faraggi D, Wactawski-Wende J, Townsend JM, Lynch AM, Perkins NJ, Mumford SL, Galai N. Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. Lancet. 2014 Jul 5;384(9937):29-36. doi: 10.1016/S0140-6736(14)60157-4. Epub 2014 Apr 2.
- Background Seamon LG, Cohn DE, Henretta MS, Kim KH, Carlson MJ, Phillips GS, Fowler JM. Minimally invasive comprehensive surgical staging for endometrial cancer: Robotics or laparoscopy? Gynecol Oncol. 2009 Apr;113(1):36-41. doi: 10.1016/j.ygyno.2008.12.005. Epub 2009 Jan 24.
- Background Silver RM, Edwin SS, Trautman MS, Simmons DL, Branch DW, Dudley DJ, Mitchell MD. Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide. J Clin Invest. 1995 Feb;95(2):725-31. doi: 10.1172/JCI117719.
- Background Smith GC. Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies. Am J Obstet Gynecol. 2001 Feb;184(3):489-96. doi: 10.1067/mob.2001.109735.
- Background Smith GC, Shah I, Pell JP, Crossley JA, Dobbie R. Maternal obesity in early pregnancy and risk of spontaneous and elective preterm deliveries: a retrospective cohort study. Am J Public Health. 2007 Jan;97(1):157-62. doi: 10.2105/AJPH.2005.074294. Epub 2006 Nov 30.
- Background Souter D, Harding J, McCowan L, O'Donnell C, McLeay E, Baxendale H. Antenatal indomethacin--adverse fetal effects confirmed. Aust N Z J Obstet Gynaecol. 1998 Feb;38(1):11-6. doi: 10.1111/j.1479-828x.1998.tb02949.x.
- Background Subtil D, Goeusse P, Houfflin-Debarge V, Puech F, Lequien P, Breart G, Uzan S, Quandalle F, Delcourt YM, Malek YM; Essai Regional Aspirine Mere-Enfant (ERASME) Collaborative Group. Randomised comparison of uterine artery Doppler and aspirin (100 mg) with placebo in nulliparous women: the Essai Regional Aspirine Mere-Enfant study (Part 2). BJOG. 2003 May;110(5):485-91. doi: 10.1046/j.1471-0528.2003.t01-1-02097.x.
- Background Vainio M, Kujansuu E, Iso-Mustajarvi M, Maenpaa J. Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. BJOG. 2002 Feb;109(2):161-7. doi: 10.1111/j.1471-0528.2002.01046.x.
- Background Vainio M, Riutta A, Koivisto AM, Maenpaa J. Prostacyclin, thromboxane A and the effect of low-dose ASA in pregnancies at high risk for hypertensive disorders. Acta Obstet Gynecol Scand. 2004 Dec;83(12):1119-23. doi: 10.1111/j.0001-6349.2004.00396.x.
- Background Valero De Bernabe J, Soriano T, Albaladejo R, Juarranz M, Calle ME, Martinez D, Dominguez-Rojas V. Risk factors for low birth weight: a review. Eur J Obstet Gynecol Reprod Biol. 2004 Sep 10;116(1):3-15. doi: 10.1016/j.ejogrb.2004.03.007.
- Background Van Marter LJ, Leviton A, Allred EN, Pagano M, Sullivan KF, Cohen A, Epstein MF. Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy. Pediatrics. 1996 May;97(5):658-63.
- Background Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003 Jun 15;110(5-6):255-8. doi: 10.1016/s0049-3848(03)00379-7.
- Background Vermillion ST, Robinson CJ. Antiprostaglandin drugs. Obstet Gynecol Clin North Am. 2005 Sep;32(3):501-17. doi: 10.1016/j.ogc.2005.04.006.
- Background Werler MM, Sheehan JE, Mitchell AA. Maternal medication use and risks of gastroschisis and small intestinal atresia. Am J Epidemiol. 2002 Jan 1;155(1):26-31. doi: 10.1093/aje/155.1.26.
- Background Yu Y, Cheng Y, Fan J, Chen XS, Klein-Szanto A, Fitzgerald GA, Funk CD. Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition. J Clin Invest. 2005 Apr;115(4):986-95. doi: 10.1172/JCI23683. Epub 2005 Mar 17.
- Meltzer GY, Duttweiler LP, Saleem S, Shankar K, Mazariegos M, Tshefu A, Patterson JK, Chomba E, Carlo WA, Goudar S, Derman R, Patel AB, Hibberd PL, Liechty E, Essamai F, Asturias E, Babineau DC, Moore J, Tuholske C, Zimmer A, Coull BA, McClure E, Goldenberg RL, Krebs N, Hoffman MK, Wylie BJ. Aspirin and Preterm Birth Among Pregnant People With Increased Heat Exposure: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 May 1;9(5):e2611402. doi: 10.1001/jamanetworkopen.2026.11402.
- Mwenechanya M, Tembo AM, Chomba E, Hoffman MK, Goudar SS, Moore JL, Metgud MC, Somannavar MS, Okitawutshu J, Lokangaka AL, Tshefu AK, Bose CL, Bauserman MS, Figueroa L, Garces A, Krebs NF, Jessani S, Saleem S, Goldenberg RL, Kurhe K, Das P, Patel AB, Hibberd PL, Nyongesa P, Esamai F, Bucher SL, Goco N, Hemingway-Foday JJ, Babineau DC, McClure EM, Silver RM, Derman RJ, Carlo WA; ASPIRIN Study Group Collaborators. Does Adherence Modify Low-Dose Aspirin Effects in Pregnancy? Post Hoc Analysis From a Multi-Centre Trial. BJOG. 2026 Apr 19. doi: 10.1111/1471-0528.70244. Online ahead of print.
- Bucher S, Nowak K, Otieno K, Tenge C, Marete I, Rutto F, Kemboi M, Achieng E, Ekhaguere OA, Nyongesa P, Esamai FO, Liechty EA. Birth weight and gestational age distributions in a rural Kenyan population. BMC Pediatr. 2023 Mar 8;23(1):112. doi: 10.1186/s12887-023-03925-2.
- Hoffman MK, Goudar SS, Kodkany BS, Metgud M, Somannavar M, Okitawutshu J, Lokangaka A, Tshefu A, Bose CL, Mwapule A, Mwenechanya M, Chomba E, Carlo WA, Chicuy J, Figueroa L, Garces A, Krebs NF, Jessani S, Zehra F, Saleem S, Goldenberg RL, Kurhe K, Das P, Patel A, Hibberd PL, Achieng E, Nyongesa P, Esamai F, Liechty EA, Goco N, Hemingway-Foday J, Moore J, Nolen TL, McClure EM, Koso-Thomas M, Miodovnik M, Silver R, Derman RJ; ASPIRIN Study Group. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial. Lancet. 2020 Jan 25;395(10220):285-293. doi: 10.1016/S0140-6736(19)32973-3.
- Hoffman MK, Goudar SS, Kodkany BS, Goco N, Koso-Thomas M, Miodovnik M, McClure EM, Wallace DD, Hemingway-Foday JJ, Tshefu A, Lokangaka A, Bose CL, Chomba E, Mwenechanya M, Carlo WA, Garces A, Krebs NF, Hambidge KM, Saleem S, Goldenberg RL, Patel A, Hibberd PL, Esamai F, Liechty EA, Silver R, Derman RJ. A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study. BMC Pregnancy Childbirth. 2017 May 3;17(1):135. doi: 10.1186/s12884-017-1312-x.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Aspirin | Small molecule | 81 mg | — |
Indications
No indication recorded.