Hypertensive Disorders of PregnancyOPHELIA-PPNCT07841795
Ophthalmic Artery Doppler in the Puerperium After Hypertensive Disorders of Pregnancy (OPHELIA-PP)
An observational study of Hypertensive Disorders of Pregnancy and Pre-eclampsia, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
Hypertensive disorders of pregnancy frequently fail to resolve at delivery. A substantial proportion of women remain hypertensive at the six-week postnatal review, postpartum eclampsia occurs days to weeks after birth, and a minority show persisting renal dysfunction. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hypertensive Disorders of Pregnancy, Pre-eclampsia, Postpartum Hypertension
- How many people
- 366 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2027to 1 Mar 2028
- How long will I take part?
- 6 Weeks
- Phase
- Observational
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 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women delivering at participating tertiary obstetric centres, comprising those whose pregnancy was complicated by a hypertensive disorder or who developed de novo postpartum hypertension, and a concurrently enrolled comparison group of women with normotensive pregnancies.
Who may be able to join
- Exposed Cohort
- Age 18 years or older
- Hypertensive disorder of pregnancy diagnosed by ISSHP 2018 criteria: pre-eclampsia, gestational hypertension, chronic hypertension, chronic hypertension with superimposed pre-eclampsia, eclampsia or HELLP syndrome
- Or de novo postpartum hypertension or pre-eclampsia arising within 48 hours of delivery after a normotensive pregnancy
- Delivery at a participating centre, at any gestational age and by any mode of delivery
- Written informed consent
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- Comparison cohort:
- Age 18 years or older
- Normotensive pregnancy without hypertensive complications
- Delivery at a participating centre
- Written informed consent
- Enrolled concurrently at a 1:2 ratio relative to the exposed cohort, matched by age band and parity
Who cannot join
- Known ocular disease affecting the orbital circulation: glaucoma, proliferative retinopathy, previous orbital surgery or ocular trauma
- Known carotid artery stenosis or previous cerebrovascular event
- Significant structural heart disease
- Known chronic kidney disease stage 3 or above
- Diabetes mellitus with end-organ damage
- Inability to undergo the examination because of clinical instability or refusal
- Foreseeable inability to complete follow-up
- Inability to give informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Azienda Ospedaliero-Universitaria Policlinico Umberto I, Department of Maternal and Child Health and Urological Sciences
Roma, RM, 00161
Giuseppe Rizzo, Prof, 39 06 49971, giuseppe.rizzo@uniroma1.it
Ilenia Mappa, Prof, 39 06 49971, ilenia.mappa@uniroma1.it
About this study
Official title: Ophthalmic Artery Doppler in the Puerperium and Maternal Outcomes After Hypertensive Disorders of Pregnancy: a Prospective Cohort Study
Hypertensive disorders of pregnancy frequently fail to resolve at delivery. A substantial proportion of women remain hypertensive at the six-week postnatal review, postpartum eclampsia occurs days to weeks after birth, and a minority show persisting renal dysfunction. Attendance at postnatal follow-up is nonetheless poor and specialist resources are limited, so a simple bedside test that identified the women whose cardiovascular recovery is incomplete would allow surveillance to be targeted.
Ophthalmic artery Doppler is non-invasive, takes about five minutes and requires only a linear transducer already present in obstetric units. Its antenatal performance is well characterised, but a systematic review by this group (PROSPERO CRD420261488689) identified only three studies in thirty years addressing the postpartum period, two of which included a normotensive comparator, totalling 131 women. None reported a threshold or any measure of diagnostic accuracy, and none recorded antihypertensive treatment at the time of scanning.
This prospective cohort study will measure ophthalmic artery Doppler indices at four timepoints between delivery and three months in women with hypertensive disorders of pregnancy and in normotensive controls, and will determine whether the peak systolic velocity ratio measured 24 to 48 hours after delivery predicts persistent hypertension at the six-week postnatal review.
Read the detailed description
Design. Prospective observational cohort study with consecutive recruitment and a concurrently enrolled normotensive comparison group, conducted at a coordinating tertiary centre and participating satellite centres.
Non-interventional nature. Ophthalmic artery Doppler does not alter clinical management, which follows existing institutional protocols throughout. Doppler results are not communicated to the clinicians responsible for the participant, who remain blinded to them for the duration of the study, so that the measurement cannot influence the outcome it is intended to predict. An alerting procedure is nonetheless in place for incidental findings of clinical relevance.
Assessments. Ophthalmic artery Doppler is performed at 24 to 48 hours (T0), 7 to 10 days (T1), six weeks (T2) and three months (T3) after delivery, with a telephone follow-up at six months (T4). Blood pressure is measured at each visit using a standardised protocol with a validated automated device. Estimated glomerular filtration rate and albumin-to-creatinine ratio are obtained at six weeks.
Doppler protocol. Participants are examined supine with the eyes closed after five minutes of rest. A 7.5-9 MHz linear transducer is placed on the closed upper eyelid without pressure on the globe. The ophthalmic artery is identified superior and medial to the optic nerve, 10-15 mm from the posterior scleral wall. Pulsed-wave sampling uses an insonation angle below 20 degrees, a 2 mm sample gate, a 50 Hz wall filter and a depth of 3.0-4.5 cm, with mechanical index kept at or below 0.3 and insonation time under one minute per eye in accordance with the ALARA principle. Three to five consecutive waveforms of similar morphology are recorded, two cycles are measured per eye, both eyes are examined, and the mean of the two eyes is analysed. First and second peak systolic velocities, their ratio, end-diastolic velocity, resistance index, pulsatility index and mean velocity are recorded.
Antihypertensive exposure. The drug, dose and the interval in minutes between the last administration and the Doppler examination are recorded at every timepoint. This addresses the principal methodological limitation of the existing literature, in which no comparative study documented treatment at the time of scanning although these agents are known to modify the waveform acutely.
Reproducibility. A random 10% sample of examinations is independently re-read by a second blinded operator.
Sample size. The calculation is driven by the precision of the sensitivity estimate for the primary outcome. Assuming a sensitivity of 80% estimated with a 95% confidence interval half-width of 10%, 62 women with the outcome are required; at an anticipated prevalence of persistent hypertension of 30%, this requires 207 women assessed at six weeks, and 244 to be enrolled allowing for 15% attrition. The comparison group of 122 normotensive women gives 90% power at alpha 0.05 to detect a standardised mean difference of 0.40, well below the effects reported in the existing comparative studies.
- Conditions
- Hypertensive Disorders of Pregnancy, Pre-eclampsia, Postpartum Hypertension, Puerperal Disorders, Maternal Haemodynamics
- Keywords
- ophthalmic artery, Doppler ultrasonography, postpartum period, pre-eclampsia, peak systolic velocity ratio, ; postnatal follow-up
- Medical subject headings
- Pre-Eclampsia, Puerperal Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Hypertensive disorders of pregnancy | Women whose pregnancy was complicated by a hypertensive disorder diagnosed by ISSHP 2018 criteria - pre-eclampsia, gestational hypertension, chronic hypertension, chronic hypertension with superimposed pre-eclampsia, eclampsia or HELLP syndrome - or who developed de novo postpartum hypertension or pre-eclampsia within 48 hours of delivery after a normotensive pregnancy. Recruited consecutively after delivery at a participating centre, at any gestational age and by any mode of delivery. Ophthalmic artery Doppler is performed at 24-48 hours, 7-10 days, six weeks and three months postpartum, with a telephone follow-up at six months. Blood pressure is measured at each visit and renal function assessed at six weeks. Doppler results are not disclosed to the clinicians responsible for care. | |
| Normotensive comparison group | Women with a normotensive pregnancy and no hypertensive complication, recruited concurrently at the same centres in a 1:2 ratio relative to the exposed cohort and matched by age band and parity. They undergo the same ophthalmic artery Doppler protocol at the same timepoints, with the same blood pressure measurement procedure, and serve as the reference group for the comparison of Doppler indices during the puerperium. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy of ophthalmic artery peak systolic velocity ratio for persistent postpartum hypertension
Accuracy of the ophthalmic artery peak systolic velocity ratio measured 24-48 hours after delivery for the prediction of persistent postpartum hypertension.
Description: area under the receiver operating characteristic curve, with the optimal threshold and its sensitivity and specificity. Persistent hypertension is defined as systolic blood pressure at or above 140 mmHg and/or diastolic at or above 90 mmHg in the absence of antihypertensive treatment, or at or above 130/80 mmHg while on treatment.
Time frame: outcome ascertained at six weeks (42 ± 7 days) postpartum.
Measured: Six weeks (42 +/- 7 days) after delivery
Secondary outcomes (8)
Difference in ophthalmic artery Doppler indices between cohorts24-48 hours, 7-10 days, 6 weeks and 3 months postpartum
Difference between women with hypertensive disorders of pregnancy and normotensive women in first peak systolic velocity, second systolic peak, peak systolic velocity ratio, end-diastolic velocity, resistance index, pulsatility index and mean velocity, expressed as adjusted mean differences and as standardised mean differences for comparability with the published literature.
Measured: 24-48 hours, 7-10 days, 6 weeks and 3 months postpartum
Accuracy of peak systolic velocity ratio for postpartum renal dysfunction
Area under the receiver operating characteristic curve, sensitivity and specificity of the peak systolic velocity ratio measured 24-48 hours after delivery for renal dysfunction, defined as estimated glomerular filtration rate below 60 mL/min/1.73 m2 and/or urinary albumin-to-creatinine ratio above 3 mg/mmol.
Measured: 6 weeks after delivery
Accuracy of peak systolic velocity ratio for readmission for hypertension
Area under the receiver operating characteristic curve, sensitivity and specificity of the peak systolic velocity ratio for unplanned readmission for hypertension or its complications, including postpartum pre-eclampsia and eclampsia.
Measured: 6 weeks after delivery
Accuracy of peak systolic velocity ratio for escalation of antihypertensive treatment
Area under the receiver operating characteristic curve, sensitivity and specificity of the peak systolic velocity ratio for the need to start, increase or add antihypertensive medication after discharge.
Measured: 6 weeks after delivery
Ophthalmic Artery Peak Systolic Velocity Ratio in Women Receiving Versus Not Receiving Antihypertensive Treatment
Peak systolic velocity ratio (second to first systolic peak, unitless) measured by transorbital pulsed-wave Doppler ultrasound as the mean of both eyes, reported separately for women receiving and women not receiving antihypertensive medication at the time of the examination.
Measured: 24-48 hors after delivery
Correlation Between Ophthalmic Artery Peak Systolic Velocity Ratio and Time Since Last Antihypertensive Dose
Spearman correlation coefficient (unitless, range -1 to 1) between the peak systolic velocity ratio measured by transorbital pulsed-wave Doppler ultrasound and the interval in minutes between the last administration of antihypertensive medication and the Doppler examination, in women receiving treatment.
Measured: 24-48 hours after delivery
Difference in Doppler indices between hypertensive phenotypes
Comparison of ophthalmic artery indices between pre-eclampsia, gestational hypertension, chronic hypertension and de novo postpartum hypertension, and between severe and non-severe disease.
Measured: 6 weeks after delivery
Intra- and inter-observer reproducibility of the measurement
Reproducibility of the ophthalmic artery measurement in the postpartum setting, expressed as intraclass correlation coefficient and Bland-Altman limits of agreement, assessed on a random 10% sample independently re-read by a second blinded operator.
Measured: Throughout the study period,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hypertensive Disorders of PregnancyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 366 participants (estimated)
- Target duration
- 6 Weeks
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giuseppe Rizzo, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07841795
- Sponsor's protocol ID
- OPHELIA-PP-2026
- Acronym
- OPHELIA-PP
- Status last verified
- Sep 2026
- First submitted
- 16 Sep 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the published results, together with the data dictionary, the study protocol, the statistical analysis plan and the analysis code, will be made available to investigators whose proposed use of the data has been approved by the study steering committee.
Publications
de Oliveira CA, de Sa RA, Velarde LG, da Silva FC, doVale FA, Netto HC. Changes in ophthalmic artery Doppler indices in hypertensive disorders during pregnancy. J Ultrasound Med. 2013 Apr;32(4):609-16. doi: 10.7863/jum.2013.32.4.609.
PubMed 23525385Lau KG, Baloi M, Dumitrascu-Biris D, Nicolaides KH, Kametas NA. Changes in ophthalmic artery Doppler during acute blood-pressure control in hypertensive pregnant women. Ultrasound Obstet Gynecol. 2022 Feb;59(2):185-191. doi: 10.1002/uog.23755.
PubMed 34358385Alves Borges JH, Goes DA, de Araujo LB, Dos Santos MC, Debs Diniz AL. Prospective study of the hemodynamic behavior of ophthalmic arteries in postpartum preeclamptic women: A doppler evaluation. Hypertens Pregnancy. 2016;35(1):100-11. doi: 10.3109/10641955.2015.1116553. Epub 2016 Feb 6.
PubMed 26852911Giannina G, Belfort MA, Cruz AL, Herd JA. Persistent cerebrovascular changes in postpartum preeclamptic women: a Doppler evaluation. Am J Obstet Gynecol. 1997 Nov;177(5):1213-8. doi: 10.1016/s0002-9378(97)70042-5.
PubMed 9396921