Community Level Interventions for Pre-eclampsia

Study Overview
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Brief Summary
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This project is being undertaken to test the hypothesis that implementing a community based package of care for women with hypertensive disorders of pregnancy will result in overall improvement in maternal and neonatal outcomes. This is based on the premise that there are three main modifiable reasons why women (and their fetuses/newborns) die due to pregnancy complications: 1) delays by the woman herself in recognizing the seriousness of her condition; 2) delays in her being assessed and then transported to a center capable of providing effective and life-saving interventions; and 3) delays in the health facility in providing those interventions. The treatments for pre-eclampsia that are poorly accessed in LMIC are 1) magnesium sulfate (MgSO4) for prevention and treatment of the grand mal seizures of eclampsia; 2) oral antihypertensive medication to lower maternal BP to reduce the risk of stroke. The CLIP pilot and definitive cRCT will investigate whether the community level intervention including implementation of the CLIP package (oral antihypertensive therapy when indicated, intramuscular (i.m.) MgSO4 when indicated; and appropriate referral to an CEmOC facility when indicated) of care will reduce the incidence of all-cause maternal morbidity and mortality.

Detailed Description
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We have designed a two-phased community (including PHC-level) cRCT encompassing both rural and urban settings to be fully powered in each of: Ogun State, Nigeria Maputo and Gaza Province, Mozambique Hyderabad and Matiari districts in Sindh Province, Pakistan. Belgaum and Bagalkot districts in Karnataka State, India The trial will be phased from the Pilot CLIP trial to Definitive CLIP trial on the basis of a satisfactory rate of use (≥50%) of the CLIP 'package of care' in appropriate women in all countries but Mozambique. Mozambique will be unique in that they will rely on an extended period of feasibility to pilot test all Trial systems and tools before directly beginning a definitive trial. Foregoing the Pilot in Mozambique was felt to be appropriate based on their experience with community-based surveillance and will ensure timelines of the trial are met within a manageable budget. For all other countries, use of the package in the Pilot phase will be defined as appropriate referral (urgent or non-urgent) to a facility able to provide comprehensive emergency obstetric care (CEmOC) in appropriate women during the first six months of the Pilot CLIP trial. A primary component of the CLIP intervention is antenatal risk assessment guided by the PIERS on teh Move mHealth decision aid. The CLIP version of the PIERS on the Move tool (CLIP POM) integrates the miniPIERS predictive score and a clinical data collection system into a single application. Community health workers in each country will assess women according to the visit protocol, entering clinical data into the CLIP POM mobile application. The application will provide recommendations for care according to meeting one of the trigger events listed below, as per this protocol. Triggers identified that will indicate treatment and/or transport (urgently, defined as within 4hrs) to a CEmOC facility are as follows: Unconsciousness (MgSO4 if sBP ≥160 mmHg [to be reasonably sure that the unconsciousness is associated with severe pre-eclampsia and not due to obstetric sepsis], urgent transport) Signs of recent stroke or seizure (methyldopa if sBP ≥160 mmHg [to ensure BP is not lowered too much], MgSO4, urgent transport) Significant vaginal bleeding (MgSO4 if sBP ≥140 mmHg [presumed abruption associated with severe pre-eclampsia], urgent transport). No fetal movements felt in the previous 12 hrs (urgent transport [a threshold for identifying at risk fetuses that are alive at the time of screening] 39) sBP ≥160 mmHg (or dBP ≥ 110 mmHg in Nigeria only) (methyldopa, MgSO4, urgent transport [consistent with severe pre-eclampsia]) Heavy proteinuria (≥4+ by dipstick - predictive of stillbirth in miniPIERS cohort, urgent transport) miniPIERS predicted probability ≥25% (MgSO4, urgent transport) Shock index >1.7 in Nigeria only (the Shock index is a ratio of pulse/sBP; high shock index is an indication of poor prognosis in women with postpartum haemorrhage) Non-urgent transport (by non-ambulance services), meaning assessment at a CEmOC facility within 24 hours, will be advised for all women with non-severe hypertension (sBP 140-159 mmHg) who do not meet criteria for one of the above 7/8 triggers. In Mozambique and Pakistan additional CLIP triggers based on use of the audio oximeter will also be included in the POM decision aid. As with the original miniPIERS model, the enhanced model including SpO2 uses a risk threshold of ≥25% predicted probability to identify high-risk cases. Recommendations based on the updated miniPIERS model will include treatment with MgSO4 and urgent referral. An additional independent trigger of SpO2<93% will also be used in Mozambique and Pakistan to indicate urgent referral. In Nigeria where the updated Microlife CRADLE VSA blood pressure device is being used additional triggers will be included for severe diastolic blood pressure or severe shock index to coincide with the traffic light warning signs included in this device.

Official Title
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The CLIP (Community Level Interventions for Pre-eclampsia) Cluster Randomized Controlled Trial

Conditions
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Pre-eclampsia, Hypertension, Pregnancy Induced

Intervention / Treatment
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* Behavioral: Community Engagement
* Device: PIERS on the Move mHealth decision aid
* Drug: Magnesium Sulfate
* Drug: Methyldopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all consenting pregnant women Exclusion Criteria: non-pregnant

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The CLIP intervention consists of (i) community engagement including community leaders, the women of the communities themselves, and their mothers, husbands, and mothers-in-law, regarding pre-eclampsia, its origins, symptoms, signs, and potential consequences, pre-permissions for maternal transport, and fundraising activities around transport and treatment costs; (ii) provision of HDP oriented antenatal care through CLIP visits and use of CLIP PIERS on the Move mHealth tool (for risk stratification), and (iii) use of the CLIP package for women with a CLIP 'trigger' (i.e., oral antihypertensive therapy (methyldopa) when indicated, intramuscular (i.m.) magnesium sulfate when indicated; and appropriate referral to an CEmOC facility when indicated) | Behavioral: Community Engagement<br>* The primary objective of the community engagement activities in CLIP will be to create awareness and action around the prevention of maternal morbidity and mortality due to pre-eclampsia/eclampsia. Community engagement involves the collective action of individuals, families, religious leaders, policy makers,<br>Device: PIERS on the Move mHealth decision aid<br>* This mHealth application is to be used by community health workers in intervention clusters to guide collection of relevant clinical data during antenatal visits. This clinical data is used to generate a risk estimate for any women with hypertension based on the miniPIERS (Pre-eclampsia Integrated Estimate of Risk) clinical risk prediction model. This risk estimate in combination with other pre-defined treatment triggers (severe hypertension (>160mmHg systolic) or proteinuria (>3+ dipstick); absence of fetal movements for greater than 12 hours; signs of recent stroke of seizure) are collected in the app and based on this data recommendations for care of the woman are provided.<br>* Other names: CLIP mHealth tool;Drug: Magnesium Sulfate<br>* Women identified in intervention clusters by the community health worker during a study visit as being at high risk of- or having recently experienced- an eclamptic seizure will be given 10 g intramuscular magnesium sulfate prior to transfer to a nearby facility for further care.<br>* Other names: MgSO4;Drug: Methyldopa<br>* Women identified in intervention clusters as having severe hypertension (systolic greater than 160 mmHg) by the community health worker during a study visit will be given 750 mg of oral methyldopa prior to transfer to a nearby facility for further care.<br>* Other names: Aldomet;|
| No Intervention: Control<br>Current standard of antenatal care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal or Perinatal death or morbidity | Combined outcome including any one of the following: Maternal death (number of deaths during or within 42d of pregnancy or last contact day if contact not maintained to 42d/1000 identified pregnancies); termed Maternal Death Rate. Maternal morbidity (number of women with ≥1 life-threatening complication of pregnancy (ie eclampsia, major PPH requiring surgical intervention, obstetric sepsis, stroke, etc) during or within 42d of pregnancy or last contact day if contact not maintained to 42d) / 1000 identified pregnancies Perinatal death (stillbirth [≥20+0 and/or ≥500g], early neonatal mortality [d0-7 of postnatal life] and late neonatal mortality [d8-28 of postnatal life] /1000 identified pregnancies) Neonatal morbidity (occurrence of any non-lethal morbidity (ie severe breathing difficulty, severe feeding difficulty, seizure, lethargy, coma, hypothermia, skin or umbilical stump infection, jaundice, etc) during 0-28d of postnatal life /1000 identified pregnancies) | within 42 days of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth preparedness and complication readiness | as measured by any three of the following: (1) arranged for transport; (2) obtained prior permission for transport should emergency arise; (3) saved money for obstetric care; (4) identified skilled birth attendant; (5) identified facility for delivery. This will evaluate the success of community engagement. | from 20 weeks gestation to delivery | 
| Facility births | number of women presenting for delivery in a CEmONC facility in control vs intervention clusters | from 20 weeks gestation to delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cluster randomized controlled trial, pre-eclampsia, eclampsia, maternal mortality