Contact information
Type
Scientific
Primary contact
Dr Mario Merialdi
ORCID ID
Contact details
World Health Organization
20 Avenue Appia
Geneva-27
CH 1211
Switzerland
merialdim@who.int
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
WHO/A35048
Study information
Scientific title
Acronym
Study hypothesis
The specific aim of the proposed study is to determine whether administration of 1000 mg of vitamin C and 400 iu of vitamin E, from the second trimester, to high risk women, is associated with a reduction in the incidence of preeclampsia.
Ethics approval
Ethics approval received from the World Health Organization (WHO) Scientific and Ethical Review Board and Ethical Review Committee in 2004; renewed approval in 2006.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Pre-eclampsia
Intervention
Randomised to Vitamin C (1000 mg) and Vitamin E (400 IU), or placebo to be taken daily until delivery.
Intervention type
Supplement
Phase
Not Specified
Drug names
Vitamin C and Vitamin E
Primary outcome measure
Occurrence of pre-eclampsia: defined as gestational, severe gestational hypertension and proteinuria:
1. Gestational hypertension will be defined as two or more readings of diastolic blood pressure greater than or equal to 90 mmHg (using Korotkoff V) taken more than or equal to 4 hours, but less than 168 hours apart, and occurring after 20 weeks of pregnancy or in the early postnatal period, and excluding labour
2. Severe gestational hypertension will be defined as two recordings of diastolic blood pressure of 110 mmHg or higher at least 4 hours apart, (but less than 168 hours apart) or one recording of diastolic blood pressure greater than 120 mmHg
3. Proteinuria will be defined as excretion of greater than 300 mg protein in 24 hours or 2 readings of greater than or equal to 1+ on dipstick of Mid-Stream Urine (MSU)/Catheter Specimen Urine (CSU) where 24 hour collection is not available
Secondary outcome measures
1. Pre-eclampsia as defined in the context of the WHO calcium supplementation trial:
Pre-eclampsia is defined as hypertension associated with proteinuria. Hypertension is defined as blood pressure greater than or equal to 140 mmHg systolic and/or 90 mmHg diastolic occurring in two occasions at least four hours to a week apart after the 20th week of pregnancy. Diastolic blood pressure will be measured at the 5th Korotkoff sound, which is the disappearance of the sounds. Proteiunuria is defined if protein in urine is greater than or equal to 300 mg in 24 hours urine specimen or corresponding level of 1+ or more on dipstick.
2. Principal neonatal outcomes:
2.1. Death, intrauterine or neonatal before discharge from the hospital
2.2. Low birthweight, defined as below 2.5kg
2.3. Small for gestational age as defined by WHO guidelines: infants below the 10th percentile of the birth-weight-for-gestational age, sex specific, single/twins curve
3. Other secondary outcome measures (also adequately powered to detect important effects):
3.1. Preterm birth (before 37+0 weeks)
3.2. Use of health care resources: antenatal inpatient days
3.3. Gestational age at delivery
Overall trial start date
27/07/2004
Overall trial end date
27/07/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
14^+0 - 21^+6 weeks pregnant women with one or more of the following risk factors:
1. Chronic hypertension - diastolic Blood Pressure (BP) greater than 90 mmHg
2. Pre-gestational diabetes
3. Arterial, venous or small vessel thrombosis in any organ tissue
4. Unexplained death of morphologically normal foetus at or beyond ten weeks gestation
5. Premature births before 34 weeks due to pre-eclampsia, eclampsia or severe placental insufficiency
6. Unexplained consecutive spontaneous abortions before ten weeks
7. Chronic renal disease
8. Multiple pregnancy
9. Past history of pre-eclampsia, eclampsia, HELLP syndrome (Haemolysis, Elevated Liver enzyme Levels and low Platelet count)
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
1790
Participant exclusion criteria
1. Inability to give informed consent
2. Women taking supplements containing greater than 200 mg vitamin C or greater than 50 IU vitamin E daily dose
3. Women taking warfarin
Recruitment start date
27/07/2004
Recruitment end date
27/07/2006
Locations
Countries of recruitment
India, Peru, Viet Nam
Trial participating centre
World Health Organization
Geneva-27
CH 1211
Switzerland
Sponsor information
Organisation
UNDP/UNFPA/WHO/World Bank - Special Programme of Research, Development and Research Training in Human Reproduction
Sponsor details
20 Avenue Appia
Geneva-27
CH 1211
Switzerland
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
United Nations Development Programme (UNDP)/United Nations Population Fund (UNFPA)/World Health Organization (WHO)/World Bank - Special Programme of Research, Development and Research Training in Human Reproduction (HRP)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list