Personalized Medicine for Pregnant Women: Novel Metabolomic and Proteomic Biomarkers to Detect Pre-eclampsia and Improve Outcome.
试验速览
- 阶段
- 不适用
- 发起方
- Louise Kenny
- 入组人数
- 5,000
- 试验地点
- 6
- 主要终点
- Pre-eclampsia.
研究概览
简要总结
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.
详细描述
Sample size calculations have been considered extensively and given the complexity of the study; there is no single simple solution. For the purpose of sample size estimation in the overall study, we used a binary outcome and associated measures of sensitivity and likelihood ratio as determinants of the value of these tests. Although the predictive algorithms will produce a continuous risk score, the use of a categorical outcome fits with the final binary decision process (to treat or not to treat) based on the risk score. Based on the lowest estimated prevalence of pre-eclampsia of 3% and a test sensitivity of 93% and a test specificity of 97%, then to be 90% certain that the true specificity of the patient population is no less than 95%, a sample size of 4,800 participants is required. Thus, allowing for patient dropout, a study population of 5,000 women is needed.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Nulliparous.
- •Singleton pregnancy, between 9+0 and 16+6 weeks' gestation.
- •Signed informed consent.
排除标准
- •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.
结局指标
主要结局
Pre-eclampsia.
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
- Early onset pre-eclampsia(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Multisystem complications of pre-eclampsia(Between 20 weeks´gestation and 6 weeks after birth)
- Pre-eclampsia with severe fetal or neonatal complications(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Major neonatal morbidity in preterm infants(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Major neonatal morbidity in term infants(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Pre-eclampsia with severe maternal complications(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Early onset SGA(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Preeclampsia with either severe maternal complication or severe fetal or neonatal complications(Followed for the duration of hospital stay, an expected average of 6 weeks)
- SGA with severe fetal or neonatal complications(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Spontaneous preterm birth with PPROM(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Early onset spontaneous preterm birth(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Spontaneous preterm birth with severe fetal or neonatal complications(Followed for the duration of hospital stay, an expected average of 6 weeks)
- Spontaneous preterm birth without PPROM(Followed for the duration of hospital stay, an expected average of 6 weeks)