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Community Level Interventions for Pre-eclampsia (CLIP)

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ClinicalTrials.gov Identifier: NCT01911494
Recruitment Status : Active, not recruiting
First Posted : July 30, 2013
Last Update Posted : November 19, 2018
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Olabisi Onabanjo University
Centro de Investigacao em Saude de Manhica
Aga Khan University
Jawaharlal Nehru Medical College
Information provided by (Responsible Party):
Peter von Dadelszen, University of British Columbia

Brief 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.


Condition or disease Intervention/treatment Phase
Pre-eclampsia Hypertension, Pregnancy Induced Behavioral: Community Engagement Device: PIERS on the Move mHealth decision aid Drug: Magnesium Sulfate Drug: Methyldopa Not Applicable

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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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The CLIP (Community Level Interventions for Pre-eclampsia) Cluster Randomized Controlled Trial
Study Start Date : September 2013
Actual Primary Completion Date : May 2018
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Experimental: Intervention
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
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,

Device: PIERS on the Move mHealth decision aid
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.
Other Name: CLIP mHealth tool

Drug: Magnesium Sulfate
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.
Other Name: MgSO4

Drug: Methyldopa
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 Name: Aldomet

No Intervention: Control
Current standard of antenatal care



Primary Outcome Measures :
  1. Maternal or Perinatal death or morbidity [ Time Frame: within 42 days of pregnancy ]

    Combined outcome including any one of the following:

    1. 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.
    2. 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
    3. 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)
    4. 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)


Secondary Outcome Measures :
  1. Birth preparedness and complication readiness [ Time Frame: from 20 weeks gestation to delivery ]
    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.

  2. Facility births [ Time Frame: from 20 weeks gestation to delivery ]
    number of women presenting for delivery in a CEmONC facility in control vs intervention clusters


Other Outcome Measures:
  1. Pre-eclampsia knowledge [ Time Frame: from 20 weeks gestation to time of delivery ]
  2. Post-trial seizures [ Time Frame: within 42 days of pregnancy ]
    Assessment of post-trial start eclamptic seizures in control vs intervention clusters to assess effectiveness of community dosing of magnesium sulfate

  3. Cost-effectiveness [ Time Frame: within 42 days of pregnancy ]
    Of the CLIP package against QALYs

  4. Adverse effects [ Time Frame: within 42 days of pregnancy ]
    Adverse effects of magnesium include injection site hematoma or infection, and respiratory depression

  5. Functional disability [ Time Frame: within 6 months of delivery ]
    Index measurement of functional ability, including ability to care for baby, do household chores and return to work within 6 months of delivery measured at two to four week intervals postpartum.



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Ages Eligible for Study:   15 Years to 49 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • all consenting pregnant women

Exclusion Criteria:

  • non-pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01911494


Locations
India
Jawaharlal Nehru Medical College, Karnataka Lingayat Education University
Belgaum, Karnataka, India
Mozambique
Centro de Investigacaoem Saude de Manhica (CISM)
Maputo, Mozambique
Nigeria
Centre for Research in Reproductive Health, Olabisi Onabanjo University
Sagamu, Ogun State, Nigeria
Pakistan
Aga Khan University
Karachi, Sindh, Pakistan
Sponsors and Collaborators
University of British Columbia
Bill and Melinda Gates Foundation
Olabisi Onabanjo University
Centro de Investigacao em Saude de Manhica
Aga Khan University
Jawaharlal Nehru Medical College
Investigators
Principal Investigator: Peter von Dadelszen, MBChB, DPhil University of British Columbia

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Peter von Dadelszen, Study Principal Investigator, University of British Columbia
ClinicalTrials.gov Identifier: NCT01911494     History of Changes
Other Study ID Numbers: H12-03497
F12-01593 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
First Posted: July 30, 2013    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: November 2018

Keywords provided by Peter von Dadelszen, University of British Columbia:
cluster randomized controlled trial
pre-eclampsia
eclampsia
maternal mortality

Additional relevant MeSH terms:
Eclampsia
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications
Hypertension
Vascular Diseases
Cardiovascular Diseases
Magnesium Sulfate
Methyldopa
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics
Central Nervous System Depressants
Anti-Arrhythmia Agents
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Tocolytic Agents
Reproductive Control Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents