Evaluation of a novel device in the management of high blood pressure and shock in pregnancy in low-resource settings

• Register: ISRCTN
• Last refreshed on: 20 March 2023
• Main ID: ISRCTN41244132
• Date of registration: 02/02/2016
• Prospective Registration: Yes
• Primary sponsor: Kings College London (UK)
• Public title: Evaluation of a novel device in the management of high blood pressure and shock in pregnancy in low-resource settings
• Scientific title: Evaluation of the CRADLE vital sign alert device in the management of hypertension and shock in pregnancy in low-resource settings to reduce maternal mortality and morbidity: a stepped wedge randomised controlled trial
• Date of first enrolment: 01/03/2016
• Target sample size: 10
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN41244132
• Study type: Interventional
• Study design: Two-phased multicentre stepped wedge cluster randomised controlled trial (Prevention)
• Phase: Not Specified

Countries of recruitment

Ethiopia, Haiti, India, Malawi, Sierra Leone, Uganda, Zambia, Zimbabwe

Contacts

• Name: Andrew Shennan

Key inclusion & exclusion criteria

Inclusion criteria:
1. All pregnant/postpartum women living in Trial Area catchment areas* within the trial time frame
2. Women identified as pregnant or within the 6 weeks post-partum period, presenting for antenatal, intrapartum or postpartum care

*Catchment areas will be defined by local investigators, and include all possible outreach facilities that result in women being assessed and referred to a defined central facility/ies, prior to randomisation and remain constant throughout the study period.

Exclusion criteria: There will be no exclusion criteria, including age of women, as, from an ethical and logistical standpoint, all pregnant women (including those below the age of 16 years) should have access to blood pressure measurement during pregnancy. Data are to be collected at a cluster level rather than at an individual level.

Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Maternal mortality and major morbidity from the three leading causes of maternal death worldwide: obstetric haemorrhage, sepsis and pre-eclampsia
Pregnancy and Childbirth

Intervention(s)

This is a two-phased multicentre stepped wedge cluster randomised controlled trial of the introduction of the CRADLE package (Vital Signs device and training package) to maternity care settings in eight low income countries.

Due to the stepped wedge trial design, each randomisation cluster crosses over from control to the CRADLE intervention at two-monthly intervals over the 21 month trial period. For the first two-month interval no cluster has the intervention and by 21 month all clusters will have the intervention. The intervention effect is determined by comparing data points in the intervention section of the wedge with those in the control section. This design has been selected to evaluate the intervention in a pragmatic fashion. Individual randomisation would be logistically difficult and would not measure impact and transferability at a population level. The stepped wedge design is useful where phased implementation is preferable because of logistical and practical constraints. Our LIC collaborators have indicated that this is their preferred means of participation, as a phased introduction of the intervention is more reflective of current implementation programs.

The intervention consists of the CRADLE VSA device, a device that measures blood pressure and heart rate and calculates shock index, and a simple education package that describes how to use the device. The simple education package consists of two specific short animated films on the use of the device and management of hypertension and shock and posters and alert cards. The CRADLE VSA will be incorporated into routine antenatal care as all women should have blood pressure measured regularly in the antenatal period. Therefore there is no specified treatme

Primary Outcome(s)

Primary outcome measures as of 01/04/2016 (Added 09/12/2016):
The primary outcome is the rate of a composite of maternal mortality or major morbidity (one of maternal death, eclampsia or emergency hysterectomy with no double counting) per 10,000 deliveries. We will report the effect of the intervention on the primary endpoint, on each of the three components, and on the secondary endpoints specified. Results will be reported firstly as odds ratios, with risk ratios as a secondary comparison if the appropriate models converge. The components of the primary outcome are defined as:
1. Maternal death is defined as death during pregnancy or within 42 days of delivery (or last contact day if contact not maintained to 42 days).
2. Eclampsia is defined as occurrence of generalised convulsions or coma with increased BP during pregnancy, labour or within 42 days of delivery in the absence of epilepsy or another condition predisposing to convulsions
3. Emergency Hysterectomy is defined as surgical removal of all or part of the uterus

Primary outcome measures as of 29/02/2016:
1. Maternal death, defined as death during pregnancy or within 42 days of delivery (or last contact day if contact not maintained to 42 days)
2. Eclampsia, defined as occurrence of generalised convulsions or coma with increased blood pressure during pregnancy, labour or within 42 days of delivery in the absence of epilepsy or another condition predisposing to convulsions
3. Emergency Hysterectomy, defined as surgical removal of all or part of the uterus

Following the completion of the three month pilot phase from November 2015 to February 2016 there have been minor prospective amendments to the protocol prior to the start of the main trial in March 2016. Given the variable access to intensive care beds and low prevalence of stroke observed across our trial sites in the pilot these outcomes will not be included in the primary composite outcome. They will continue to be measured as secondary outcomes. The event rate of our existing composite primary outcome components (Maternal death, eclampsia, emergency hysterectomy) remain sufficient to maintain planned statistical power.

Original primary outcome measures:
1. Maternal death, defined as death during pregnancy or within 42 days of delivery (or last contact day if contact not maintained to 42 days)
2. Intensive Care Unit admission, defined as any admission to intensive care unit or an equivalent highest-level care environment within the trial area (or referral to the highest level care facility outside of the area) in areas where Intensive Care Unit does not exist
3. Eclampsia, defined as occurrence of generalised convulsions or coma with increased blood pressure during pregnancy, labour or within 42 days of delivery in the absence of epilepsy or another condition predisposing to convulsions
4. Stroke, defined as hemiparesis and/or blindness developed during pregnancy or in the 42 days postpartum lasting greater than 48 hours
5. Hysterectomy, defined as surgical removal of all or part of the uterus

All primary and secondary outcomes are measured consistently across the site area throughout trial duration so that the overall impact of intervention can be determined over the 21 month trial period. Interim analysis is not feasible due to the stepped wedge design.

Secondary Outcome(s)

Secondary outcome measures as of 29/02/2016:
Maternal Secondary outcome measures:
1. Intensive Care Unit admission, defined as any admission to a specific intensive care unit or an equivalent highest-level care environment within the trial area (or referral to the highest level care facility outside of the area) in areas where Intensive Care Unit does not exist
2. Stroke, defined as hemiparesis and/or blindness developed during pregnancy or in the 42 days postpartum lasting greater than 48 hours
3. Cause of intensive care admission
4. Cause of maternal death
5. Cause of emergency hysterectomy
5. Place of eclamptic fit
6. Place of maternal death

These additional secondary outcome measures have been added following the pilot experience in an effort to determine the potential benefit of the device on these outcomes.

Neonatal Secondary outcome measures
We recognise that the CRADLE intervention may reduce neonatal mortality and morbidity, but have not been chosen to evaluate these as primary outcomes, as the intervention is designed specifically to identify maternal health complications. Many of these occur postpartum and will not directly influence perinatal outcomes. Acquisition of detailed perinatal data within LIC settings would be a substantial additional cost. However, we will collect secondary outcomes including:
1. Number of stillbirths
2. Number of neonatal deaths


Original secondary outcome measures:
We recognise that the CRADLE intervention may reduce neonatal mortality and morbidity, but have not been chosen to evaluate these as primary outcomes, as the intervention is designed specifically to identify maternal health complications. Many of these occur postpartum and will not directly influence perinatal outcomes. Acquisition of detailed perinatal data within LIC settings would be a substantial additional cost. However, we will collect secondary outcomes including:
1. Number of stillbirths
2. Number of neonatal deaths

All primary and secondary outcomes are measured consistently across the site area throughout trial duration so that the overall impact of intervention can be determined over the 21 month trial period. Interim analysis is not feasible due to the stepped wedge design.

Secondary ID(s)

N/A

MR/N006240/1

Source(s) of Monetary Support

Medical Research Council, Department Of Biotechnology (India), Department for International Development (UK) Global Research Programme

Ethics review

Status:
Approval date:
Contact:

1. Biomedical Sciences, Dentistry, Medicine and Natural & Mathematical Sciences Research Ethics Subcommittee, 26/08/2015, ref: LRS-14/15-1484 2. Individual ethics approvals have been sought and finalised from each of our international partners

Results

• Results available: Yes
• Date Completed: 01/03/2018