IMproved PRegnancy Outcome by Early Detection (IMPROvED)

Louise Kenny

Status: Unknown

Conditions: Pregnancy Complications; Pregnancy, High-risk; Pre-eclampsia; Pregnancy

Study type: Observational

Funder types: Other

Identifiers

NCT01891240

Study Protocol v. 8.0 20122013

Project no: 305169 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 5,000 estimated patients

Sex: Female

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

5,000 participants in 1 patient group

First time, low risk mothers

Description:

The study population will consist of first time, low risk mothers attending for antenatal care in one of the participating clinical centres.