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Low-dose aspirin in the prevention of pre-eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial.

ABSTRACT: BACKGROUND:Low-dose aspirin (LDA) has been proposed as a safe and inexpensive prophylactic agent. Studies in European/Western populations have shown promising results indicating that LDA can reduce the occurrence of pre-eclampsia (PE) in women with identifiable risk factors. However, few controlled trials, particularly large randomized controlled trials, have been performed in Asian populations. The aim of this project is to evaluate the effect of LDA for PE prevention on high-risk pregnant women in China, where PE is highly prevalent and the LDA supply status is commonly suboptimal. METHODS/DESIGN:An open-label, multicentre randomized controlled trial is being conducted at 13 tertiary hospitals in 11 provinces in China. A total of 1000 eligible women with high-risk factors for developing PE according to their medical histories are being randomized into two groups: a control group (n?=?500) and an intervention group (n?=?500). Women with high-risk factors, such as a history of PE, chronic hypertension, type 1 or 2 diabetes, advanced maternal age, obesity, family history of PE or nulliparity are eligible. The control group is advised to undergo routine examinations, whereas the intervention group undergoes the routine examinations and receives LDA. LDA (100 mg/d) should be prescribed at night, initiating from early pregnancy (12-20 weeks of gestation) and lasting until 34 weeks of gestation. Demographic data and clinical endpoint outcomes, as well as biological samples (e.g., maternal blood, cord blood, amniotic fluid and placental samples), will be collected. The primary outcome is the occurrence of PE, and the secondary outcomes include maternal and neonatal outcomes and maternal biomarker levels. DISCUSSION:This is the first and largest multicentre randomized controlled trial to assess the effect of LDA in preventing PE in a Chinese population. The results will potentially influence the prenatal care recommendations in China regarding intervention with LDA for PE. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02797249 . Registered on 7 June 2016.

SUBMITTER: Lin L

PROVIDER: S-EPMC6218975 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Low-dose aspirin in the prevention of pre-eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial.

Lin Li L Zhu Yuchun Y Li Boya B Yang Huixia H

Trials 20181106 1

<h4>Background</h4>Low-dose aspirin (LDA) has been proposed as a safe and inexpensive prophylactic agent. Studies in European/Western populations have shown promising results indicating that LDA can reduce the occurrence of pre-eclampsia (PE) in women with identifiable risk factors. However, few controlled trials, particularly large randomized controlled trials, have been performed in Asian populations. The aim of this project is to evaluate the effect of LDA for PE prevention on high-risk pregn ...[more]

PMID: 30400937

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Project description:IntroductionPregnancy in sickle cell disease is fraught with many complications including pre-eclampsia (PE) and intrauterine growth restriction (IUGR). Previously, we found an abnormality in prostacyclin-thromboxane ratio in sickle cell pregnant women, a situation that is also found in non-sickle pregnancies with PE and unexplained IUGR. Low-dose aspirin (LDA) has been shown to reduce the incidence of PE and IUGR in high-risk women by reducing the vasoconstrictor thromboxane while sparing prostacyclin, in effect 'correcting' the ratio. It has been found to be safe for use in pregnancy but has not been tested in sickle cell pregnancy. We hypothesise that LDA will reduce the incidence of IUGR and PE in pregnant haemoglobin SS (HbSS) and haemoglobin SC (HbSC) women.Methods and analysisThis is a multisite, double blind, randomised controlled trial, comparing a daily dose of 100 mg aspirin to placebo, from 12 to 16 weeks' gestation until 36 weeks, in Lagos state, Nigeria. Four hundred and seventy-six eligible pregnant HbSS and HbSC women will be recruited consecutively, randomly assigned to either group and followed from recruitment until delivery. The primary outcome will be the incidence of birth weight below 10th centile for gestational age on INTERGROWTH 21 birth weight charts, or incidence of miscarriage or perinatal death. Secondary outcomes will include PE, maternal death, preterm delivery, perinatal death, number of crises, need for blood transfusion and complications such as infections and placental abruption. Analysis will be by intention to treat and the main treatment effects will be quantified by relative risk with 95% CI, at a 5% significance level.Ethical approvalEthical approval has been granted by the Health Research and Ethics committees of the recruiting hospitals and the National Health Research and Ethics Committee. Study findings will be presented at conferences and published appropriately.Trail registration numberPACTR202001787519553; Pre-results.

Project description:IntroductionPre-eclampsia is an important cause of death and complication for pregnant women and perinatal infant. Low-dose aspirin has been most commonly used to prevent pre-eclampsia in high-risk pregnant women. Recently, heparins have also been used alone or in combination with aspirin to prevent pre-eclampsia. However, the optimal doses and combination therapy of aspirin and heparins are not well established. Therefore, we aim to compare aspirin, heparins and their combination to prevent pre-eclampsia in a network meta-analysis.Methods and analysisWe will search the following electronic databases from the date of database establishment to 8 January 2019: PubMed, Embase, Cochrane Library, Web of Science and ProQuest. We will also search additional studies manually. There will be no restriction on the language of publications. Only randomised clinical trials will be eligible in our network meta-analysis. We will include pregnant women who have been recommended for aspirin according to the standard of the American Congress of Obstetricians and Gynecologists, or were designated as high risk in some recent studies. We will include studies comparing the effects of any single or combination of aspirin and heparins with placebo or observation or another intervention in pregnancy. We will include studies that reported one of the following outcomes: pre-eclampsia, severe pre-eclampsia, preterm delivery, perinatal death and full-term pre-eclampsia with delivery at ≥37 weeks. Traditional pairwise meta-analysis will be performed initially, and then network meta-analysis will be performed using frequency analysis method. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings.Ethics and disseminationThis network meta-analysis does not require ethical certification. An overview and information on the prevention of pre-eclampsia in high-risk pregnant women will be provided by this network meta-analysis.Prospero registration numberCRD42018084248.

Project description:BackgroundPreterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth.Methods and findingsWe performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates.ConclusionsIn this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth.Trial registrationDutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.

Project description:BACKGROUND: An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. METHODS: A further analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. RESULTS: The median number of severe PE/E cases in the past year was just 5 (range 0-42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at regional and specialized hospitals (p?<?0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There was a significant difference between doctors and midwives on only one item: continued use of anti-hypertensives after convulsions are controlled. CONCLUSIONS: Drugs and supplies needed to treat severe PE/E are widely available at EmONC facilities in Afghanistan, but providers lack knowledge in some areas, especially concerning the use of MgSO4 and diazepam. Providers who have specialized training or work at larger facilities are better at managing cases of severe PE/E. The findings suggest a need to clarify service delivery guidelines, offer refresher training, and reinforce best practices with supervision and reinforcement.

Project description:BackgroundPreterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation.MethodsASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970.FindingsFrom March 23, 2016 to June 30, 2018, 14?361 women were screened for inclusion and 11?976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups.InterpretationIn populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development.

Dataset Information

Low-dose aspirin in the prevention of pre-eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial.

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Low-dose aspirin in the prevention of pre-eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial.

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