Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04535804 |
| Other study ID # |
KS20253 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
October 2020 |
| Est. completion date |
September 2022 |
Study information
| Verified date |
August 2020 |
| Source |
Shanghai First Maternity and Infant Hospital |
| Contact |
qiaoling Du, doctorate |
| Phone |
15021628612 |
| Email |
duqiaoling[@]51mch.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objective: This study intends to carry out a randomized double-blind clinical trial study of
aspirin in the treatment of pregnancy with adenomyosis to reduce the incidence of preterm
delivery, and provide a new therapeutic target for the prevention and treatment of premature
birth and adverse pregnancy outcomes, and fill in the blank of effective prevention of
premature delivery in pregnancy with adenomyosis at home and abroad Application value and
social and economic benefits of the bed.
Methods: a randomized double-blind clinical trial was used in this study. In Shanghai first
maternal and child health care hospital, the pregnant women who meet the requirements of the
group will be given full informed consent. By using a random, double-blind research method,
1-550 digital computers are randomly divided into two groups, with two groups of digital
coding placebo and aspirin. From 12 weeks of gestation, 100 mg of placebo or low-dose aspirin
was given orally (2 tablets a time, twice a day, before going to bed) to 36 weeks of
gestation.
Observe the outcome ① Main outcome measures: preterm delivery: delivery less than 37 weeks
gestational weeks, premature delivery. The specific classification includes: A. extremely
premature delivery, gestational age 28-32 weeks; B. early preterm birth, delivery gestational
weeks 32-34 gestational weeks; C. late preterm birth, 34-36 gestational weeks.
② Secondary outcome measures: abortion, gestational diabetes mellitus, gestational
hypertension, placental disorders, SGA / FGR, premature rupture of membranes, postpartum
hemorrhage, mode of delivery, etc.
The follow-up contents were as follows
- Routine prenatal examination, blood pressure, fetal size, vaginal bleeding, etc.
- Coagulation factor index: prothrombin time Pt, activated partial thrombin time
APTT, thrombin time TT, fibrinogen FIB, D-dimer
- Immune related indexes: antiphospholipid antibody, CA125 ④ Inflammatory index:
routine blood test + CRP
- Detection of cervical length by B-ultrasound ⑥ Pregnancy complications:
gestational diabetes mellitus, gestational hypertension and placental
disorders ⑦ Birth outcome: gestational weeks, birth weight, FGR,
premature delivery, mode of delivery, NICU rate, etc.
Description:
Research background:
Adenomyosis (AD) is a benign uterine disease with endometrial glands and stroma invading into
the myometrium, accompanied by hyperplasia and hypertrophy of uterine smooth muscle cells,
which leads to abnormal uterine structure and function. In non pregnancy period, the main
manifestations are diffuse enlargement of uterus, dysmenorrhea, menorrhagia, menorrhagia,
which can lead to infertility. In recent years, with the delay of childbearing age, the
incidence of adenomyosis in pregnancy is increasing gradually. The incidence of adenomyosis
in the general population reached 20.9%, while the incidence of adenomyosis was higher in
recurrent abortion and assisted reproduction, reaching 38.2% and 34.7% respectively. Studies
have shown that adenomyosis is associated with early preterm delivery, late preterm delivery,
low birth weight infants, very low birth weight infants, and small for gestational age
infants. Patients with adenomyosis are prone to hypertensive disorder complicating pregnancy,
intrauterine infection, abnormal placenta, and increased cesarean section, postpartum
hemorrhage and abnormal fetal position.
Aspirin is widely used in the treatment of immune system diseases and the prevention of
cerebrovascular diseases because of its anti-inflammatory and anti platelet aggregation
effects. Aspirin is more and more widely used in obstetrics and Gynecology, such as recurrent
abortion caused by antiphospholipid antibody syndrome, recurrent abortion related to abnormal
uterine artery blood flow and unexplained recurrent abortion. Since 1980, aspirin has been
widely recommended for the prevention of pregnancy with high risk factors of preeclampsia and
intrauterine growth restriction, and it has been confirmed that aspirin is effective in the
prevention of pregnancy It is safe in clinical application. The inflammatory environment of
adenomyosis is closely related to the initiation of preterm delivery, but whether aspirin can
benefit pregnant women with adenomyosis is still lacking.
Research plan
1. Study population Inclusive criteria: ① Singleton; ② in line with the diagnosis of
adenomyosis in pregnancy; ③ no history of chronic diseases and definite diagnosis of
endocrine diseases, including diabetes, hypertension, obesity, antiphospholipid
syndrome; ④ informed consent and voluntary participation in this study.
Exclusion criteria: ① twins / multiple births; ② induced labor for medical reasons; ③
allergic to aspirin or other salicylates, tetracycline drugs or any other components of
drugs; ④ patients with mental disorders; ⑤ transferred to hospital.
Withdrawal criteria: Subjects withdraw informed consent; subjects request to withdraw
from the trial.
Termination of the experiment: unacceptable adverse events occurred; the subjects
voluntarily asked to withdraw from the trial; the protocol was violated; the researcher
/ ethics committee considered it necessary for the subjects to stop the trial.
2. Diagnostic criteria of adenomyosis: according to pre pregnancy and early pregnancy
transvaginal ultrasound diagnosis. The diagnostic criteria of transvaginal ultrasound
for adenomyosis include: (a) ectopic endometrial glands and stroma, (b) myometrium
hyperplasia, hypertrophy, and increased blood vessels.
3. Sample size calculation: the incidence of preterm delivery in pregnant women with
adenomyosis was about 21.63% (Mette R. Bruun et al. 2018). It is expected that the
incidence of preterm birth in patients with adenomyosis during pregnancy will be reduced
by 40% after aspirin intervention, that is, the incidence of premature delivery in the
intervention group will be about 12.98%. Assuming that the test level α is 0.05, the
test efficiency is 0.8, and one-sided test, 236 sample sizes are estimated for the
intervention group and the control group by using the sample size estimation software
pass. Considering the loss of follow-up rate of about 10%, the sample size of
intervention group and control group was about 262 cases. Therefore, 550 pregnant women
were recruited in this study.
4. Statistical analysis plan: the statistical analysis in the study is based on the
principle of intention to treat (ITT), that is, all the subjects involved in the study
participate in the statistical analysis. Chi square test or unpaired t test was used to
analyze the difference between the intervention group and the control group. In the chi
square test, if the theoretical frequency of cells was less than 5, Fisher exact
probability method was used, and the Mann Whitney U test was used for quantitative
variables that did not conform to normal distribution. Chi square test was used to
analyze the difference of preterm birth rate between intervention group and control
group. Logistic regression model was used to estimate the relative risk value and 95%
confidence interval (95% confidence interval) of preterm birth between the two groups.
The choice of statistical analysis method for secondary outcome indicators was
consistent with that in primary outcome analysis. SAS viya was used as the analysis
software in the study, and the difference was statistically significant when p < 0.05.
research implementation process: research steps (describe the data collection content and
method according to the time node) 2020.10-2020.12：we distributed recruitment advertisements,
prepared placebos and aspirin, screened and enrolled patients, signed informed consent, and
arranged outpatient follow-up of enrolled patients; 2021.01-2021.06：150 cases of pregnant
women with adenomyosis were planned to be enrolled, and the registration and follow-up of the
patients were done well; 2021.07-2021.12：150 cases of pregnant women with adenomyosis were
planned to be enrolled; the experimental data were summarized gradually; the information of
defect was recorded; 2022.01-2022.06：150 cases of pregnancy with adenomyosis were planned to
be enrolled, the pregnancy outcomes of the pregnant women were counted, and the case report
forms were completed; 2022.07-2022.09： we plan to complete the work of 50 cases of pregnancy
with adenomyosis, analyze the data statistically, write papers and final reports.
Risk of study: placebo had no effect on subjects; adverse reactions of aspirin mainly
included gastrointestinal reactions, risk of fetal teratogenesis before 12 weeks of
pregnancy, and risk of bleeding during pregnancy. However, since 1980, aspirin has been
widely used in the prevention of pregnancy with high risk factors of preeclampsia and fetal
growth restriction, which proves that the probability of adverse reactions of low-dose
aspirin is very low, no teratogenic effect is found, and it has clinical safety.
Benefits of the study: expected to reduce the incidence of preterm birth and improve adverse
pregnancy outcomes. In order to explore the prevention and treatment of premature delivery
and adverse pregnancy outcomes, it is necessary to provide a new therapeutic target, fill in
the blank of the effective prevention of premature birth treatment of pregnancy combined with
adenomyosis at home and abroad, which may reduce the medical costs related to pregnancy
complications and adverse pregnancy outcomes, as well as the cost of dealing with adverse
pregnancy outcomes. This study has important clinical application value and social and
economic benefits.
Recruitment and protection measures of subjects There are recruitment advertisements in this
study, and other documents are provided; Protective measures for the subjects: in order to
reduce the adverse reactions of aspirin as far as possible, we used aspirin enteric coated
tablets, 50mg, twice a day, the dosage belongs to low dose. From 12 weeks of gestation to 36
weeks of gestation. If you have bleeding during pregnancy, you need to stop taking aspirin,
and you can continue to take aspirin after the bleeding disappears. The number of follow-up
visits during pregnancy is roughly the same as that of general prenatal examination (about 10
times), without additional visits; about 5ml more blood will be drawn for examination on the
day of establishing pregnancy card, and the extra examination cost will be borne by the
research group; we will arrange experienced doctors to take charge of the whole pregnancy
examination of the subjects and keep communication at any time. We will pay more attention to
the subject's gastrointestinal reaction, tinnitus, erythema, liver and kidney function and
other discomfort during each birth examination. If there is any abnormality, we will take the
following measures: (1) immediately stop your experiment if the condition requires; (2) be
responsible for the treatment of your adverse drug reactions; (3) give appropriate economic
compensation according to the degree of your injury.
Informed consent process: the subject's informed consent work is in charge of a specially
assigned person, who will provide sufficient and easy to understand information to the
pregnant women who meet the inclusion conditions; the subjects of informed consent are all
those with independent ability, and they will not be able to participate in this project if
they have no independent ability; there will be no pressure on pregnant women who meet the
inclusion conditions in the process of informed consent. In the process of participating in
the research, it will ensure that research participants get timely information (including
their rights, safety and health).
