Vitamins in Preeclampsia (VIP): a multicentre randomised clinical trial of vitamin C and E supplementation in pregnancy for the prevention of pre-eclampsia (India, Peru, Vietnam)

ISRCTN	ISRCTN86677348
DOI	https://doi.org/10.1186/ISRCTN86677348
Protocol serial number	WHO/A35048
Sponsor	UNDP/UNFPA/WHO/World Bank - Special Programme of Research, Development and Research Training in Human Reproduction
Funder	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)

Submission date: 06/06/2005
Registration date: 07/06/2005
Last edited: 25/08/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Mario Merialdi
Scientific

World Health Organization
20 Avenue Appia
Geneva-27
CH 1211
Switzerland

Email	merialdim@who.int

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	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(s)	Ethics approval received from the World Health Organization (WHO) Scientific and Ethical Review Board and Ethical Review Committee in 2004; renewed approval in 2006.
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	27/07/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	1790
Key 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)
Key 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
Date of first enrolment	27/07/2004
Date of final enrolment	27/07/2006

Locations

Countries of recruitment

India
Peru
Switzerland
Viet Nam

Study participating centre

World Health Organization

Geneva-27
CH 1211
Switzerland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan