Protocol summary
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Study aim
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prevention of occurrence of early and late preeclampsia
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Design
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Randomized clinical trial.Assessor-blinded. Two intervention groups and control group.
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Settings and conduct
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At each visit, the presence of edema or preeclampsia symptoms are noted and recorded. In addition, participants are assessed for possible aspirin side effects.
Participants are randomly selected to receive low-dose aspirin, either before 11 weeks’ gestation (optimally from the detection of the fetal heart beat) in the intervention group or after 11 weeks in the control group. The cut-off gestational age to receive aspirin is 16 weeks in the control group. In both groups, the initial dose of aspirin is 80 mg per day. In both groups, aspirin will be continued until 36 weeks or in the case of premature delivery.
At 11_13 weeks and 6 days, when the gestational age is confirmed by an ultrasound study of the CRL measurement through the fetal NT measurement, the UTA-PI of uterine arteries is assessed transabdominally. In addition, a combined test for aneuploidy screening is requested through measuring the maternal serum free β-hcG and PAPP-A.
If there are criteria in both groups including:
PAPP-A < 0.4 in the first trimester or
preeclampsia risk more than or equal1 ̸ 100 to in aneuploidy screening test or
in color doppler ultrasound (the mean UTA-PI>95th percentile or bilateral notching), the initial dose of aspirin, which is 80 mg, is changed to 150 mg per day.
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Participants/Inclusion and exclusion criteria
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The participants are pregnant women at high-risk for preeclampsia according to the ACOG and USPSTF and SMFM guidelines.
Exclusion criteria:
mentioned on he previous page.
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Intervention groups
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intervention group: early start of aspirin
Control group: routine intervention
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Main outcome variables
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Early and late preeclampsia
General information
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Reason for update
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Hello, No major change have been made in the process and metodology of the trial,except for subtleties that help the audience to better and secondly,our tudy include two main parts. The first part, which has been approed in this center,is being done and the results will be announced later. And in the from of a pilo study, as well as the feaibility of conducting the main study and solving possible problems and defects on it way, it has started with 200 participants from January 2023. The second part includes the main RCT with the same metodology. For this eason, this request was made to provide a possibility to accelerate the start of the main trial, considering the success of the pilot tudy process for feasibility in he last 6 months. Thank you very much.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20221126056611N1
Registration date:
2023-01-07, 1401/10/17
Registration timing:
prospective
Last update:
2023-12-21, 1402/09/30
Update count:
3
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Registration date
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2023-01-07, 1401/10/17
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2023-01-08, 1401/10/18
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Expected recruitment end date
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2023-12-08, 1402/09/17
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Aspirin administration from early pregnancy versus initiation after 11 week’s gestations, for prevention of pre-eclampsia in high-risk pregnant women.
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Public title
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Aspirin administration from early pregnancy versus initiation after 11 week’s gestations, for prevention of pre-eclampsia in high-risk pregnant women.
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Purpose
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Prevention
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Inclusion/Exclusion criteria
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Inclusion criteria:
The participants are pregnant women at high-risk for preeclampsia based on demographic characteristics and personal and obstetrics history, according to the ACOG and USPSTF and SMFM guidelines.
Exclusion criteria:
1) Hypersensitivity to nonsteroidal anti-inflammatory drug products
2) Asthma-rhinitis and nasal polyps
3) Sever renal or sever hepatic impairment.
4) History of gastrointestinal bleeding or active peptic ulcer disease
5) vaginal bleeding or significant hematoma on ultrasound.
6)gestational age > 16 week
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Age
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No age limit
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Gender
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Female
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Phase
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3
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Groups that have been masked
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Sample size
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Target sample size:
200
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Block Randomization, with random blocks of 4 alleles and with a size of 8.
Group A is the intervention group and B is the control group
Pregnant women who go to the prenatal clinic for pregnancy care are checked for eligibility for the study based on the study criteria. People who meet the study conditions will be candidates for the study. Based on the following blocks, they will be assigned to the intervention or control group, respectively. The intervention group or A will start aspirin earlier and at the beginning of the first trimester of pregnancy, and the participants who will be assigned to the control group, or B will receive the routine protocol of aspirin at the end of the first trimester.
How to randomly: will be based on random 4 allelic blocks:
In the execution method for randomization we use the following site to determine the sequences :
https://www.sealdenvelope.com/simple -randomiser/v1/lists
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Blinding (investigator's opinion)
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Single blinded
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Blinding description
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Due to the nature of the intervention, neither participants nor researchers can be blinded to allocation. However, assessments will be conducted by a blind analyzer for trial allocation.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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We calculated that the enrollment of 1792 patients in a 1:1 ratio of distribution (896 patients in each group) would provide the trial with a power of 90% (alpha level of 5%). If we allow for a 10% loss to follow-up, the sample size will reach 986 participants in each group. A total of 1972 eligible participants will be randomly entered into the trial arms. We proposed the sample size of 200 high-risk pregnancies for the pilot study and quality control of the center to perform the main RCT. We reached this sample size by screening 1686 pregnant women who referred to Maternal- Fetal Hospital Clinic. After taking written conscious consent, from January 2023, the trial with 100 participants in each group started with a ratio of 1:1, randomly.
Ethics committees
1
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Ethics committee
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Approval date
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2022-10-18, 1401/07/26
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Ethics committee reference number
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IR.TUMS.IKHC.REC.1401.215
Health conditions studied
1
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Description of health condition studied
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High Risk Pregnancy for preeclampsia
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ICD-10 code
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Z35
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ICD-10 code description
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Supervision of high-risk pregnancy
Primary outcomes
1
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Description
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Pre-eclampsia: Hypertension with proteinuria occurs for the first time after the 20th week of pregnancy. According to the definition of systolic blood pressure >= 140 mm Hg and diastolic blood pressure >= 90 mm Hg recorded at least during two measurements with an interval of 4 hours, along with one or more of the following that occurred for the first time after 20 weeks. given
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Timepoint
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The visit intervals of the participants are montly, up to 28 weeks, every two weeks up to 32 weeks, and weekly up to 36 weeks.
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Method of measurement
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1- Proteinuria: Excretion >=30 mg/mol in the protein/creatinine ratio; or >=300 mg in 24-hour urine; or >=2+ in urine dipstic test.2- Evidence of dysfunction of the organs of the mother's body: including acute kidney damage (creatinine >=1 mg/dL); Liver involvement (increase of transaminases including alanine aminotransferase or aspartate aminotransferase >=40 iu/l); with or without pain in the epigastric region, neurological complications (eclampsia-altered state of consciousness-blurred vision-clonus-severe headache-persistent visual scotoma); or hematological changes (thrombocytopenia-diffuse intravascular coagulopathy-hemolysis).3- Utero-placental dysfunction: such as intrauterine growth restriction, abnormal Doppler of the umbilical artery or fetal death).
Secondary outcomes
1
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Description
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Incidence of Small for gestational age (<5th centile) requiring delivery at<34 weeks and <37weeks
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Timepoint
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by performing serial biometrics during pregnancy
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Method of measurement
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ulrasound
2
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Description
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Incidence of Stillbirth or Intrauterine Fetal Death (IUFD) at≥20 weeks.
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Timepoint
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by performing serial ultrasound during pregnancy
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Method of measurement
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ultrasound
3
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Description
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Incidence of Spontaneous preterm delivery at<34 weeks and <37weeks
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Timepoint
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routine visits
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Method of measurement
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history and examination
4
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Description
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Respiratory distress syndrome, defined as need for surfactant and ventilation as a result of prematurity.
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Timepoint
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after the birth
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Method of measurement
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examination
5
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Description
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Admission to Neonate Intensive Care Unit
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Timepoint
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After the birth
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Method of measurement
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examination of newborn
6
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Description
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Incidence of placental abruption (clinically or on placental examination)
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Timepoint
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at the delivery
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Method of measurement
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clinical examination
7
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Description
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Ventilation requirement is defined as the need for positive pressure
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Timepoint
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after the birth
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Method of measurement
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clinical examination
8
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Description
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Neonatal anomaly especially gastroschisis
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Timepoint
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During the fetal period and at the time of birth
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Method of measurement
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with ultrasound during pregnancy and postnatal examinations
Intervention groups
1
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Description
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Intervention group: pregnant mothers are at high risk for preeclampsia, who take a low-dose aspirin 80 or 100 mg daily at night, at bedtime, from the beginning of the first trimester. Control group: pregnant mothers are at high risk for preeclampsia, who follow the routine protocol In the second trimester, they will have a low-dose aspirin tablet of 80 or 100 mg at night at bedtime.
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Category
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Prevention
2
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Description
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Control group: routine method of prevention of preeclampsia : in this group high risk pregnant mothers for preeclampsia who were randomly placed in this group according to the routine method that exists in the whole word and currently .It means prescribing a daily low dose aspirin pill in the above method starts from the end of the first trimester( from 12 to 14_15 weeks).
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Category
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Prevention
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Tehran University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Yes - There is a plan to make this available
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Data Dictionary
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Yes - There is a plan to make this available
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Title and more details about the data/document
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Final Report & Article
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When the data will become available and for how long
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6 months after the end of study
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To whom data/document is available
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Family Health Research Institute
Research deputy of University
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Under which criteria data/document could be used
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As final report and Manuscript
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From where data/document is obtainable
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Family Health Research Institute
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What processes are involved for a request to access data/document
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The published article is available to the public. The final report will be provided following the written request
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Comments
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