Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.who.int

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

Results - basic reporting

Publication summary

Publication citations

Editorial Notes