Community Level Interventions for Pre-eclampsia
Condition: Pre-eclampsia; Hypertension, Pregnancy Induced
MeSH terms: Eclampsia; Pre-Eclampsia; Hypertension, Pregnancy-Induced
Study type: Interventional

Summary: 
      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: 
      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:

        1. 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)

        2. Signs of recent stroke or seizure (methyldopa if sBP ≥160 mmHg [to ensure BP is not
           lowered too much], MgSO4, urgent transport)

        3. Significant vaginal bleeding (MgSO4 if sBP ≥140 mmHg [presumed abruption associated with
           severe pre-eclampsia], urgent transport).

        4. 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)

        5. sBP ≥160 mmHg (or dBP ≥ 110 mmHg in Nigeria only) (methyldopa, MgSO4, urgent transport
           [consistent with severe pre-eclampsia])

        6. Heavy proteinuria (≥4+ by dipstick - predictive of stillbirth in miniPIERS cohort,
           urgent transport)

        7. miniPIERS predicted probability ≥25% (MgSO4, urgent transport)

        8. 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.
    

Intervention name(s): Community Engagement; PIERS on the Move mHealth decision aid; Magnesium Sulfate; Methyldopa
Intervention type(s): Behavioral; Device; Drug; Drug
Intervention description(s): 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,; 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.; 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.; 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.
Other intervention name(s): CLIP mHealth tool; MgSO4; Aldomet
Intervention MeSH terms: Magnesium Sulfate; Methyldopa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: cluster randomized controlled trial; pre-eclampsia; eclampsia; maternal mortality