IMproved PRegnancy Outcome by Early Detection (IMPROvED)
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ClinicalTrials.gov Identifier: NCT01891240 |
Recruitment Status
:
Recruiting
First Posted
: July 3, 2013
Last Update Posted
: November 8, 2016
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The overall objective of the IMPROvED project is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for preeclampsia.
This will involve a multicentre, phase IIa clinical predictive study to assess and refine novel and innovative prototype tests based on emerging metabolomic and proteomic technologies developed by SMEs (small to medium size enterprise) within the consortium. The study will i) recruit 5000 first-time pregnant women; ii) establish a high calibre biobank, augmented by accurate clinical metadata; iii) determine whether prototype predictive assays and algorithms translate to the clinical environment; iv) assess potential synergy of a combined metabolomic and proteomic approach and v) progress regulatory approval and development of the selected test into the clinical arena.
Condition or disease |
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Pre-eclampsia Pregnancy Pregnancy, High-risk Pregnancy Complications |
Study Type : | Observational |
Estimated Enrollment : | 5000 participants |
Observational Model: | Case Control |
Time Perspective: | Prospective |
Official Title: | Personalized Medicine for Pregnant Women: Novel Metabolomic and Proteomic Biomarkers to Detect Pre-eclampsia and Improve Outcome. |
Study Start Date : | November 2013 |
Estimated Primary Completion Date : | October 2017 |
Estimated Study Completion Date : | April 2018 |

Group/Cohort |
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First time, low risk mothers
The study population will consist of first time, low risk mothers attending for antenatal care in one of the participating clinical centres.
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- Pre-eclampsia. [ Time Frame: 7 days after birth ]Preeclampsia is defined as gestational hypertension defined as systolic BP ≥140mmHg and/or diastolic BP ≥90mmHg (Korotkoff V) on at least 2 occasions 4h apart after 20 weeks' gestation, but before the onset of labour or postpartum systolic BP ≥140mmHg and/or diastolic BP ≥90mmHg on at least 2 occasions 4h apart with either proteinuria ≥300mg/24h or spot urine protein:creatinine ratio ≥30mg/mmol creatinine or urine dipstick protein ≥++.
- Spontaneous pre-term birth [ Time Frame: Up to 37+0 weeks´ gestation ]Spontaneous pre-term birth is defined as spontaneous preterm labour or preterm premature rupture of the membranes resulting in preterm birth at <37+0 weeks' gestation.
- Small for gestational age (SGA) [ Time Frame: Within 24 hours after birth ]The birth weight is converted to a customized centile, adjusting for gestation, maternal weight, height, parity, ethnicity and infant sex. SGA is defined as <10th customised centile.
- Early onset pre-eclampsia [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Pre-eclampsia resulting in delivery at <34+0 weeks' gestation.
- Multisystem complications of pre-eclampsia [ Time Frame: Between 20 weeks´gestation and 6 weeks after birth ]
Defined as one or more of the following:
- Acute renal insufficiency defined as new increase in serum creatinine to >100μmol/L antepartum or >130μmol/L postpartum.
- Liver disease defined as raised aspartate transaminase and/or alanine transaminase >45 IU/L and/or severe right upper quadrant or epigastric pain or liver rupture.
- Neurological problems defined as eclampsia, imminent eclampsia (severe headache with hyperreflexia and persistent visual disturbance) or cerebral haemorrhage.
- Haematological abnormalities including thrombocytopenia (platelets <100x109/L), disseminated intravascular coagulation or haemolysis, diagnosed by features on blood film (such as fragmented cells, helmet cells) and reduced haptoglobin.
- Pre-eclampsia with severe fetal or neonatal complications [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Pre-eclampsia resulting in either delivery at < 32+0 weeks' gestation or major neonatal morbidity or stillbirth or neonatal death or post-neonatal death.
- Major neonatal morbidity in preterm infants [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]
One or more of the following amongst babies delivered before 37 weeks' gestation:
Grade III or IV intraventricular haemorrhage; Chronic lung disease; Necrotizing enterocolitis; Retinopathy of prematurity stage 3 or 4; Sepsis (blood or CSF culture proven); Or cystic periventricular leukomalacia. These conditions will be defined using the Australian and New Zealand neonatal network definitions.
- Major neonatal morbidity in term infants [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]
One or more of the following amongst babies delivered at or after 37 weeks' gestation:
Grade II or III hypoxic ischaemic encephalopathy; Ventilation >24 hours; Neonatal unit care admission >4 days; Apgars < 4 at 5 minutes; Cord arterial pH <7.0 and/or base excess >-15; Or neonatal seizures.
- Pre-eclampsia with severe maternal complications [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]
The development of pre-eclampsia with one or more of the following:
Maternal death; Persistent severe hypertension (systolic blood pressure ≥170mmHg or diastolic blood pressure ≥110mmHg on more than one occasion antepartum or postpartum); Or multi-system complication (as defined in outcome above.
- Preeclampsia with either severe maternal complication or severe fetal or neonatal complications [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Pregnancies affected by severe maternal or severe fetal or neonatal complications (as defined in Major neonatal morbidity in preterm infants or Major neonatal morbidity term infants).
- Early onset SGA [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]SGA resulting in delivery at <34+0 weeks' gestation.
- SGA with severe fetal or neonatal complications [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]SGA and either delivery at <32+0 weeks' gestation or major neonatal morbidity (as defined in Major neonatal morbidity in preterm infants) or stillbirth or neonatal death or post-neonatal death.
- Early onset spontaneous preterm birth [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Spontaneous pre-term birth resulting in delivery < 34+0 weeks' gestation.
- Spontaneous preterm birth with severe fetal or neonatal complications [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Spontaneous preterm birth (PTB) resulting in either delivery at <32+0 weeks' or spontaneous PTB resulting in major neonatal morbidity (as defined in Major neonatal morbidity in preterm infants) or stillbirth or neonatal death or post-neonatal death.
- Spontaneous preterm birth with PPROM [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Spontaneous PTB following preterm premature rupture of the membranes (PPROM).
- Spontaneous preterm birth without PPROM [ Time Frame: Followed for the duration of hospital stay, an expected average of 6 weeks ]Spontaneous PTB with intact membranes at the onset of labour.
Biospecimen Retention: Samples With DNA

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Ages Eligible for Study: | 16 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Sampling Method: | Probability Sample |
Inclusion Criteria:
- Nulliparous.
- Singleton pregnancy, between 9+0 and 16+6 weeks' gestation.
- Signed informed consent.
Exclusion Criteria:
- Unsure of last menstrual period (LMP) and unwilling to have ultrasonography screening (USS) at ≤ 20 weeks.
- ≥ 3 miscarriages.
- ≥3 terminations of pregnancy.
- Known or suspected major fetal anomaly/abnormal karyotype.
- Essential hypertension treated pre-pregnancy.
- Moderate-severe hypertension at booking (BP >160/100 mmHg).
- Diabetes mellitus.
- Renal disease.
- Systemic lupus erythematosus.
- Anti-phospholipid syndrome.
- Sickle cell disease.
- HIV positive.
- Hepatitis B or C positive.
- Major uterine anomaly.
- Cervical suture in situ.
- Knife cone biopsy.
- Long-term steroids.
- Treatment with low-dose aspirin.
- Treatment with heparin/LMW heparin.
- Lack of informed consent.
After recruitment, if the woman is found to be outside the stated gestation limits for the IMPROvED 1st visit of 9 weeks 0 days to 13 weeks 6 days she will be retained in the study if she is willing to take part in the second and third visit and is otherwise eligible. There is one pre-specified criteria for discontinuation of a participant. If a woman is recruited into the IMPROvED study and later identified as having a pregnancy exclusion criterion, i.e., ≥ 3 miscarriages, ≥ 3 TOPS, or using low-dose aspirin at the time of recruitment, she shall be excluded. However, women diagnosed during the pregnancy but after recruitment with an exclusion criterion, e.g., diseases such as renal disease, anti-phospholipid syndrome, etc. shall be retained within the study. Women who are recruited but later discontinue from the study do not count towards recruitment targets for each centre. Accordingly, such dropouts must be replaced.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01891240
Ireland | |
Cork University Maternity Hospital, University College Cork | Recruiting |
Wilton, Cork, Ireland | |
Contact: Louise Kenny +353 (0)21 420 5023 l.kenny@ucc.ie | |
Netherlands | |
Erasmus Medical Center Rotterdam | Recruiting |
Rotterdam, Netherlands | |
Contact: Hans Duvekot j.j.duvekot@erasmusmc.nl | |
Sweden | |
Karolinska University Hospital Huddinge, Karolinska Institute | Recruiting |
Stockholm, Sweden | |
Contact: Karolina Kublickiene +46 735 930988 karolina.kublickiene@ki.se | |
United Kingdom | |
Liverpool Women's Hospital, University of Liverpool | Recruiting |
Liverpool, Merseyside, United Kingdom | |
Contact: Zarko Alfirevic +44 (0)151 795 9550 Zarko@liverpool.ac.uk | |
Keele University School of Medicine, Shrewsbury and Telford Hospital NHS Trust | Completed |
Shrewsbury, Shropshire, United Kingdom | |
Keele University School of Medicine, University Hospital of North Midlands | Completed |
Stoke-on-Trent, Staffordshire, United Kingdom |
Principal Investigator: | Louise Kenny, Professor | INFANT Centre, University College Cork, Ireland | |
Principal Investigator: | Philip N Baker, Professor | Keele Univeristy School of Medicine |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Louise Kenny, Professor, University College Cork |
ClinicalTrials.gov Identifier: | NCT01891240 History of Changes |
Other Study ID Numbers: |
Study Protocol v. 8.0 20122013 Project no: 305169 ( Other Grant/Funding Number: FP7-HEALTH-2012-Innovation-1 ) |
First Posted: | July 3, 2013 Key Record Dates |
Last Update Posted: | November 8, 2016 |
Last Verified: | November 2016 |
Keywords provided by Louise Kenny, University College Cork:
Diagnostic Pre-eclampsia Pregnancy outcome Mass screening Diagnostic Techniques and Procedures |
Additional relevant MeSH terms:
Eclampsia Pre-Eclampsia Pregnancy Complications Hypertension, Pregnancy-Induced |