Preeclampsia Sequential Screening Using Angiogenic Factors During First Trimester of Pregnancy (CRISP)

February 19, 2021 updated by: Daniel Orós López, Instituto de Investigación Sanitaria Aragón

STUDY PROTOCOL FOR A PROSPECTIVE, MULTICENTRE, COHORT STUDY: Preeclampsia Sequential Screening Using Angiogenic Factors During First Trimester of Pregnancy (CRISP STUDY)

Preeclampsia (PE) affects from 2 to 8% of pregnant women. Recent studies show that prevention is the best strategy to improve perinatal outcomes. Therefore, the development of new strategies for preeclampsia screening becomes essential in order to determine the individual risk for each patient, and thus, to identify those who would be candidates for receiving prophylactic treatment with low-dose aspirin from the first trimester of pregnancy. The aim of our study is to determine prospectively, during clinical practice, the predictive and preventive capacity of a model of preeclampsia sequential screening in the first trimester of pregnancy.

This is a prospective, multicentre, cohort study, with the collaboration of Hospital de la Santa Creu i Sant Pau (Barcelona), Hospital Universitario de Cruces (Bilbao), Hospital Son Llàtzer (Mallorca) and Hospital Clínico Universitario Lozano Blesa (Zaragoza). Women with a singleton pregnancy attending to the 12-week ultrasound scan at one of the maternity hospitals participating in the study between March 1st 2021 and 30th October 2021 will be recruited. Patients who accept to participate in the study will be classified into three risk groups (low-risk, moderate-risk and high risk) based on medical history, Mean Arterial Pressure (MAP), Pregnancy-Associated Plasma Protein A (PAPP-A) and Uterine Artery Pulsatility Index (UTPI). Placental Growth Factor (PlGF) will only be determined in those patients classified as intermediate risk after this first step and then reclassified in high and low-risk patients depending on its values. The number of first-trimester scans performed by these hospitals is approximately 8200 patients annually. Due to PE prevalence in our environment is around 3% of the total population, a total of 246 cases of PE are to be expected. Therefore, based on similar previous experiences, we could assume that 80% of the patients will accept to participate in the study, meaning a total sample of 6560 pregnant women.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

All the data required to carry out this study, including those derived from sonographies and blood tests, will be collected during the normal pregnancy control, without further appointments. A blood test will be requested in all pregnant women in the first appointment of pregnancy control between 9 and 13 weeks, to determine risk of chromosomal disorders according to the national protocol and it will be used this same sample to analyze angiogenic factors without requiring new blood extractions. In the first-trimester scan, the mean uterine arteries pulsatility index will be determined, as well as mean arterial pressure. In this visit, the patient will be asked about her medical history. We will offer the patients the inclusion to our study in that moment; those who agree to participate in the study will sign the informed consent. In the participants, the initial risk of PE will be calculated using maternal medical history, MAP, UTPI and PAPP-A (already used in aneuploidies screening), using the software validated to each laboratory. Patients will be classified into 3 groups:

  • Low risk of PE (<1/500)
  • Intermediate risk of PE (between 1/50 and 1/500)
  • High risk of PE (>1/50) In those patients classified as intermediate and high-risk, PlGF and s-Flt-1 will be determined from the blood samples kept in biobanks of each hospital according to the current legislation. SFlt-1 results will be analyzed at the end of the study in order to decrease the cost because there will not be used to make clinical decisions. PlGF in high-risk patients will not be considered either to reclassify those patients. In both cases, the diagnostic efficiency will be analyzed at the end of the study.

Patients in the intermediate-risk group (1/50-1/500) will be reclassified after adding PlGF levels in the predictive algorithm in 2 groups: Low risk of PE (<1/160) and High risk of PE (>1/160).

To the patients classified as high risk at any of the steps, will be offered prophylactic treatment with AcetylSalicylic acid (ASA) (150mg/24h) until 36 weeks of pregnancy, if there is not a contraindication. All data from eligible patients will be analyzed. A bivariant statistical analysis will be performed in order to assess the relationship between dependent variables (diagnose of PE and/or IUGR) and the other variables included in this study

Study Type

Observational

Enrollment (Anticipated)

6560

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Every singleton pregnancy attending during the period study

Description

Inclusion Criteria:

  • Singleton pregnancies;
  • Gestational age less than 14 weeks, estimated according to Crown-Rump Length (CRL);
  • Blood sample between 8 and 14 weeks of pregnancy;
  • Patients who accept to participate in the study and sign the informed consent

Exclusion Criteria:

  • Fetus with chromosomal disorders, major congenital malformations or congenital infections diagnosed in the first-trimester ultrasound;
  • Multiple pregnancies;
  • Non-acceptance of participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pregnant women
All singleton pregnancies that present to the 12-week scan in the Obstetrics Unit of the participant hospitals. Singleton pregnancies; Gestational age less than 14 weeks, estimated according to Crown-Rump Length (CRL); Blood sample between 8 and 14 weeks of pregnancy; Patients who accept to participate in the study and sign the informed consent.
Other: Pregnant women
All pregnant women that present to the 12-week scan in the Obstetrics Unit

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnosis of preeclampsia
Time Frame: 30 weeks
Diagnosis of preeclampsia during pregnancy following the definition of the International Society for the Study of Hypertension in Pregnancy, (ISSHP)
30 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Early-onset Preeclampsia
Time Frame: 30 weeks
Early-onset Preeclampsia: diagnosos before 34 weeks of pregnancy
30 weeks
Severe preeclampsia
Time Frame: 30 weeks
Severe preeclampsia (ISSHP)
30 weeks
Pregnancy-induced hypertension
Time Frame: 30 weeks
Pregnancy-induced hypertension
30 weeks
SGA
Time Frame: 30 weeks
Small for gestational age: birth weight below the 10th percentile
30 weeks
IUGR
Time Frame: 30 weeks
Intrauterine Growth Restriction
30 weeks
Perinatal mortality
Time Frame: 30 weeks
Perinatal mortality (>22 weeks of pregnancy - < 28 days postpartum)
30 weeks
Neonatal acidosis
Time Frame: 30 weeks
Neonatal acidosis (arterial pH <7.10 + base excess >12mEq/L)
30 weeks
Neonatal Intensive Care Unit
Time Frame: 16 weeks
Days of admission in neonatal Intensive Care Unit
16 weeks
Neonatal morbidity
Time Frame: 16 weeks
Significant neonatal morbidity: convulsions, intraventricular haemorrhage > III grade, periventricular leukomalacia, hypoxic-ischemic encephalopathy, abnormal electroencephalogram, necrotizing enterocolitis, acute renal failure (serum creatinine >1.5mg/dL) or heart failure (requiring inotropic agents).
16 weeks
Gestational age at birth
Time Frame: 30 weeks
Gestational age at birth
30 weeks
Type of delivery
Time Frame: 30 weeks
Type of delivery (vaginal, spontaneous or instrumental, cesarean section)
30 weeks
Cost of the analysis of angiogenic and antiangiogenic factors
Time Frame: 18 months
The economic cost of the analysis of angiogenic and antiangiogenic factors in euros (PlGF and sFlt-1).
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigación Sanitaria Aragón

Collaborators

Instituto de Salud Carlos III

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

March 1, 2021

Primary Completion (ANTICIPATED)

March 1, 2022

Study Completion (ANTICIPATED)

September 1, 2022

Study Registration Dates

First Submitted

February 19, 2021

First Submitted That Met QC Criteria

February 19, 2021

First Posted (ACTUAL)

February 23, 2021

Study Record Updates

Last Update Posted (ACTUAL)

February 23, 2021

Last Update Submitted That Met QC Criteria

February 19, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRISP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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