Pre-EclampsiaPhase 3PROVASNCT02174328
Prevention of Preeclampsia With Aspirin in Recipients of Donated Oocytes.
A Phase 3 study testing Acetylsalicylic acid in people with Pre-Eclampsia, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Pre-Eclampsia
- What is being tested?
- Acetylsalicylic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteSpain
- Study dates
- 21 May 2014to 20 Apr 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Obstetrics Unit of La Fe University and Politechnic Hospital
Valencia, 46026
About this study
Official title: Prevention of Preeclampsia With Aspirin Administered From the Beginning of Pregnancy in Recipients of Donated Oocytes.
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.
Read the detailed 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).
- Conditions
- Pre-Eclampsia
- Being tested
- Acetylsalicylic acid, Placebo
- Keywords
- See incidence of Pre-Eclampsia in acetylsalicylic acid group, See incidence of Pre-Eclampsia in placebo group
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetylsalicylic acidDrug
Also called ADIRO 100
Acetylsalicylic acid once a day until 36 week
PlaceboDrug
Also called Not active drug
Placebo once a day until 36 week
| Study group | Role | What they receive |
|---|---|---|
| acetylsalicylic acid | Experimental | This group will receive 1 tablet of acetylsalicylic acid (100 mg) orally daily from 5-10 weeks gestation until the end of gestation, about week 36 Receives: Drug: Acetylsalicylic acid |
| Placebo | Placebo comparator | This group will receive 1 tablet of placebo orally each day from 5-10 weeks gestation until the end of gestation, about week 36 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 42 weeks
Secondary outcomes (1)
Other complications
Determine the development of gestational hypertension, severe preeclampsia, IUGR, and preterm delivery in this group of patients.
Measured: Up to 42 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2014 (estimated)
- Study start21 May 2014
- Primary completion20 Apr 2018
- Study completion20 Apr 2018
Why it stopped: Halted prematurely due to low recruitment rate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigacion Sanitaria La Fe
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfredo Perales, PhD, Principal investigator, Hospital Universitario La Fe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02174328
- Sponsor's protocol ID
- PrOvAS001
- Acronym
- PROVAS
- Status last verified
- Apr 2019
- First submitted
- 11 Sep 2013
- Last updated
- 26 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 16158479ACOG 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. doi: 10.1016/s0029-7844(01)01747-1.
PubMed 16175681Akolekar 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.
PubMed 20101671Akolekar 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.
PubMed 21210481Akolekar 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.
PubMed 18956425Audibert 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.
PubMed 20691410Brosens 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.
PubMed 21094932Brown 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. doi: 10.1081/PRG-100104165. No abstract available.
PubMed 12044323Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, Forest JC, Giguere 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):402-414. doi: 10.1097/AOG.0b013e3181e9322a.
PubMed 20664402Imperiale 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.
PubMed 1829118Keegan 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. doi: 10.1016/j.fertnstert.2006.08.105. Epub 2007 Jan 29.
PubMed 17258714Klatsky 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):1387-1392. doi: 10.1097/AOG.0b013e3181fb8e59.
PubMed 21099607Levine 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. doi: 10.1056/NEJMoa055352.
PubMed 16957146Le 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.
PubMed 22252087Lambers 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.
PubMed 19608566
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Preeclampsia With Aspirin Administered From the Beginning of Pregnancy in Recipients of Donated Oocytes.
- ClinicalTrials.gov ID
- NCT02174328
- Acronym / sponsor ID
- PROVAS / PrOvAS001
- Conditions
- Pre-Eclampsia
- Keywords
- See incidence of Pre-Eclampsia in acetylsalicylic acid group, See incidence of Pre-Eclampsia in placebo group
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Halted prematurely due to low recruitment rate.
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Instituto de Investigacion Sanitaria La FeUniversity, hospital or other
- Study start
- 21 May 2014 (actual)
- Primary completion
- 20 Apr 2018 (actual)
- Study completion
- 20 Apr 2018 (actual)
- First posted
- 25 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| acetylsalicylic acid | Experimental | Drug: Acetylsalicylic acidThis group will receive 1 tablet of acetylsalicylic acid (100 mg) orally daily from 5-10 weeks gestation until the end of gestation, about week 36 |
| Placebo | Placebo comparator | Drug: PlaceboThis group will receive 1 tablet of placebo orally each day from 5-10 weeks gestation until the end of gestation, about week 36 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetylsalicylic acidAlso: ADIRO 100Acetylsalicylic acid once a day until 36 week | Drug | acetylsalicylic acid |
| PlaceboAlso: Not active drugPlacebo once a day until 36 week | Drug | Placebo |
Primary outcome
Occurrence of preeclampsia.
Time frame: Up to 42 weeks
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.
1 secondary outcome
Other complications
Time frame: Up to 42 weeks
Results and safety
The study was stopped early (reason given: Halted prematurely due to low recruitment rate.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2019.
- Background: PubMed 16158479Ebrashy 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: PubMed 16175681ACOG 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. doi: 10.1016/s0029-7844(01)01747-1.
- Background: PubMed 20101671Akolekar 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.
- Background: PubMed 21210481Akolekar 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.
- Background: PubMed 18956425Akolekar 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.
- Background: PubMed 20691410Audibert 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.
- Background: PubMed 21094932Brosens 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.
- Background: PubMed 12044323Brown 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. doi: 10.1081/PRG-100104165. No abstract available.
- Background: PubMed 20664402Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, Forest JC, Giguere 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):402-414. doi: 10.1097/AOG.0b013e3181e9322a.
- Background: PubMed 1829118Imperiale 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.
- Background: PubMed 17258714Keegan 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. doi: 10.1016/j.fertnstert.2006.08.105. Epub 2007 Jan 29.
- Background: PubMed 21099607Klatsky 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):1387-1392. doi: 10.1097/AOG.0b013e3181fb8e59.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo Perales, PhD principal investigator
Hospital Universitario La Fe
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acetylsalicylic acid in people with Pre-Eclampsia, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Halted prematurely due to low recruitment rate.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of preeclampsia. (time frame: Up to 42 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02174328, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2019.