Clinical trial NCT01911494: Community Level Interventions for Pre-eclampsia
Official title: The CLIP (Community Level Interventions for Pre-eclampsia) Cluster Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pre-eclampsia
Hypertension, Pregnancy Induced
Keywords: cluster randomized controlled trial
pre-eclampsia
eclampsia
maternal mortality
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: Olabisi Onabanjo University
name: Centro de Investigacao em Saude de Manhica
name: Aga Khan University
name: Jawaharlal Nehru Medical College
First posted: 2013-07-30
Enrollment: 87500
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Eligibility criteria: Inclusion Criteria:

* all consenting pregnant women

Exclusion Criteria:

* non-pregnant

Primary outcomes:
measure: Maternal or Perinatal death or morbidity
timeFrame: within 42 days of pregnancy
Secondary outcomes:
measure: Birth preparedness and complication readiness
timeFrame: from 20 weeks gestation to delivery
measure: Facility births
timeFrame: from 20 weeks gestation to delivery
Other outcomes:
measure: Pre-eclampsia knowledge
timeFrame: from 20 weeks gestation to time of delivery
measure: Post-trial seizures
timeFrame: within 42 days of pregnancy
measure: Cost-effectiveness
timeFrame: within 42 days of pregnancy
measure: Adverse effects
timeFrame: within 42 days of pregnancy
measure: Functional disability
timeFrame: within 6 months of delivery
Locations:
city: Belgaum
country: India
facility: Jawaharlal Nehru Medical College, Karnataka Lingayat Education University
state: Karnataka
city: Maputo
country: Mozambique
facility: Centro de Investigacaoem Saude de Manhica (CISM)
city: Sagamu
country: Nigeria
facility: Centre for Research in Reproductive Health, Olabisi Onabanjo University
state: Ogun State
city: Karachi
country: Pakistan
facility: Aga Khan University
state: Sindh
Study officials:
affiliation: University of British Columbia
name: Peter von Dadelszen, MBChB, DPhil
role: PRINCIPAL_INVESTIGATOR
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