Prevention of Preeclampsia With Aspirin in Recipients of Donated Oocytes.

Pre-Eclampsia Clinical Trial

— PROVAS  

Official title:

Prevention of Preeclampsia With Aspirin Administered From the Beginning of Pregnancy in Recipients of Donated Oocytes.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02174328
• Other study ID #: PrOvAS001
• Status: Terminated
• Phase: Phase 3
• Start date: May 21, 2014
• Est. completion date: April 20, 2018

Study information

• Verified date: April 2019
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of this trial is to study the occurrence of preeclampsia in recipients of donated oocytes receiving aspirin at an early stage during pregnancy and to compare the results with those obtained in patients receiving placebo.

Description:

Various markers have been proposed for the early diagnosis of preeclampsia: determination of mean arterial pressure; presence of multiple risk factors of preeclampsia; biochemical, ultrasound, and angiogenic markers; uterine artery Doppler, etc. These are used to determinate which patients have an increased risk of developing preeclampsia during gestation, and therefore carry out closer monitoring of pregnancy in this population. In addition, these markers can also identify patients at increased risk of developing other problems such as IUGR or preterm labor.

For nearly 30 years, there have been multiple studies trying to demonstrate that aspirin prevents the onset of preeclampsia with inconclusive results. However, recent studies in which aspirin was administered at an early stage (before 16 weeks of gestation) in patients at high risk of complications, have demonstrated a decrease in the incidence of this entity. Thus, administration of aspirin to patients at high risk (patients classified with a high risk of complications during pregnancy, based on markers mentioned above) seems to be useful in preventing onset of preeclampsia, IUGR and other complications, whenever it is administered at an early stage, as shown by several studies carried out so far.

The incidence of preeclampsia, IUGR and other complications of pregnancy is increased in patients undergoing treatment for ovulation induction, being much higher in recipients of donated oocytes. It appears that this increase may be explained by immunological processes. The focus lies on the interaction between HLA-C fetal antigen with the maternal natural killer cells. We postulate, therefore, that the administration of aspirin in recipients of donated oocytes at an early stage of pregnancy, may also reduce the incidence of preeclampsia in this group of patients.

Moreover, it has been observed that patients with preeclampsia exhibit lower levels of VEGF, PlGF and PAPP-A (factors involved in placental angiogenesis) and that this is accompanied by an increase in the sFlt1 (a potent PIGF and VEGF antagonist).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 81
• Est. completion date: April 20, 2018
• Est. primary completion date: April 20, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Patients over 18 years.

• Recipients of donated oocytes.

• Pregnant women.

• Single or twin gestations.

• Patients who accept the conditions of the study by signing the appropriate informed consent.

Exclusion Criteria:

• Known allergy to acetylsalicylic acid .

• Personal history of peptic ulcer.

• Triplets.

• Use of prostaglandin inhibitors within 10 days prior to baseline.

• Personal history of chronic kidney, thyroid, liver or heart disease.

• Psychiatric or cognitive pathology that prevents understanding of the conditions of informed consent.

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia

Intervention

Drug:
• Acetylsalicylic acid
Acetylsalicylic acid once a day until 36 week
• Placebo
Placebo once a day until 36 week

Locations

Country	Name	City	State
Spain	Obstetrics Unit of La Fe University and Politechnic Hospital	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (25)

ACOG Committee on Practice Bulletins--Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol. 2002 Jan;99(1):159-67. — View Citation

Akolekar R, de Cruz J, Foidart JM, Munaut C, Nicolaides KH. Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsia. Prenat Diagn. 2010 Mar;30(3):191-7. doi: 10.1002/pd.2433. — View Citation

Akolekar R, Syngelaki A, Sarquis R, Zvanca M, Nicolaides KH. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenat Diagn. 2011 Jan;31(1):66-74. doi: 10.1002/pd.2660. Erratum in: Prenat Diagn. 2011 Aug;31(8):832. — View Citation

Akolekar R, Zaragoza E, Poon LC, Pepes S, Nicolaides KH. Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2008 Nov;32(6):732-9. doi: 10.1002/uog.6244. Erratum in: Ultrasound Obstet Gynecol. 2009 Feb;33(2):249. — View Citation

Audibert F, Boucoiran I, An N, Aleksandrov N, Delvin E, Bujold E, Rey E. Screening for preeclampsia using first-trimester serum markers and uterine artery Doppler in nulliparous women. Am J Obstet Gynecol. 2010 Oct;203(4):383.e1-8. doi: 10.1016/j.ajog.2010.06.014. Epub 2010 Aug 5. — View Citation

Brosens I, Pijnenborg R, Vercruysse L, Romero R. The "Great Obstetrical Syndromes" are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011 Mar;204(3):193-201. doi: 10.1016/j.ajog.2010.08.009. Epub 2010 Nov 20. Review. — View Citation

Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2001;20(1):IX-XIV. Review. — View Citation

Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, Forest JC, Giguère Y. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010 Aug;116(2 Pt 1):402-14. doi: 10.1097/AOG.0b013e3181e9322a. — View Citation

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. — View Citation

Groeneveld E, Lambers MJ, Lambalk CB, Broeze KA, Haapsamo M, de Sutter P, Schoot BC, Schats R, Mol BW, Hompes PG. Preconceptional low-dose aspirin for the prevention of hypertensive pregnancy complications and preterm delivery after IVF: a meta-analysis with individual patient data. Hum Reprod. 2013 Jun;28(6):1480-8. doi: 10.1093/humrep/det022. Epub 2013 Mar 25. — View Citation

Imperiale TF, Petrulis AS. A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease. JAMA. 1991 Jul 10;266(2):260-4. — View Citation

Keegan DA, Krey LC, Chang HC, Noyes N. Increased risk of pregnancy-induced hypertension in young recipients of donated oocytes. Fertil Steril. 2007 Apr;87(4):776-81. Epub 2007 Jan 29. — View Citation

Klatsky PC, Delaney SS, Caughey AB, Tran ND, Schattman GL, Rosenwaks Z. The role of embryonic origin in preeclampsia: a comparison of autologous in vitro fertilization and ovum donor pregnancies. Obstet Gynecol. 2010 Dec;116(6):1387-92. doi: 10.1097/AOG.0b013e3181fb8e59. — View Citation

Lambers MJ, Groeneveld E, Hoozemans DA, Schats R, Homburg R, Lambalk CB, Hompes PG. Lower incidence of hypertensive complications during pregnancy in patients treated with low-dose aspirin during in vitro fertilization and early pregnancy. Hum Reprod. 2009 Oct;24(10):2447-50. doi: 10.1093/humrep/dep245. Epub 2009 Jul 16. — View Citation

Le Ray C, Scherier S, Anselem O, Marszalek A, Tsatsaris V, Cabrol D, Goffinet F. Association between oocyte donation and maternal and perinatal outcomes in women aged 43 years or older. Hum Reprod. 2012 Mar;27(3):896-901. doi: 10.1093/humrep/der469. Epub 2012 Jan 16. — View Citation

Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, Sibai BM, Epstein FH, Romero R, Thadhani R, Karumanchi SA; CPEP Study Group. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006 Sep 7;355(10):992-1005. Erratum in: N Engl J Med. 2006 Oct 26;355(17):1840. — View Citation

Nicolaides KH. A model for a new pyramid of prenatal care based on the 11 to 13 weeks' assessment. Prenat Diagn. 2011 Jan;31(1):3-6. doi: 10.1002/pd.2685. — View Citation

Pecks U, Maass N, Neulen J. Oocyte donation: a risk factor for pregnancy-induced hypertension: a meta-analysis and case series. Dtsch Arztebl Int. 2011 Jan;108(3):23-31. doi: 10.3238/arztebl.2011.0023. Epub 2011 Jan 21. — View Citation

Poon LC, Akolekar R, Lachmann R, Beta J, Nicolaides KH. Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11-13 weeks. Ultrasound Obstet Gynecol. 2010 Jun;35(6):662-70. doi: 10.1002/uog.7628. — View Citation

Ruano R, Fontes RS, Zugaib M. Prevention of preeclampsia with low-dose aspirin -- a systematic review and meta-analysis of the main randomized controlled trials. Clinics (Sao Paulo). 2005 Oct;60(5):407-14. Epub 2005 Oct 24. Review. — View Citation

Salha O, Sharma V, Dada T, Nugent D, Rutherford AJ, Tomlinson AJ, Philips S, Allgar V, Walker JJ. The influence of donated gametes on the incidence of hypertensive disorders of pregnancy. Hum Reprod. 1999 Sep;14(9):2268-73. — View Citation

Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med. 2007 Aug 2;357(5):477-87. Review. — View Citation

Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab. 2002 Apr;87(4):1762-7. — View Citation

Söderström-Anttila V, Tiitinen A, Foudila T, Hovatta O. Obstetric and perinatal outcome after oocyte donation: comparison with in-vitro fertilization pregnancies. Hum Reprod. 1998 Feb;13(2):483-90. — View Citation

Söderström-Anttila V. Pregnancy and child outcome after oocyte donation. Hum Reprod Update. 2001 Jan-Feb;7(1):28-32. Review. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Inflammatory mediators involved in angiogenesis.	Another objective is to determine if aspirin, through blockade of cyclooxygenase-2, could act in addition to reducing the synthesis of thromboxane 2, altering or diminishing the formation of various inflammatory mediators involved in angiogenesis.	Up to 42 weeks
Primary	Occurrence of preeclampsia.	The main objective is to study the occurrence of preeclampsia in recipients of donated oocytes receiving aspirin at an early stage during pregnancy, and to compare the results with those obtained in patients receiving placebo.	Up to 42 weeks
Secondary	Other complications	Determine the development of gestational hypertension, severe preeclampsia, IUGR, and preterm delivery in this group of patients.	Up to 42 weeks