High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Preventio

Phase 3

Completed

• Conditions: Prevention of pre-eclampsia; Pregnancy and Childbirth; Gestational [pregnancy-induced] hypertension with significant proteinuria

• Registration Number: ISRCTN23781770
• Lead Sponsor: Ottawa Hospital Research Institute (OHRI) (Canada)

Brief Summary

2013 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/24349782 protocol 2018 Results article in https://www.ncbi.nlm.nih.gov/pubmed/30209050 results 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33851221/ (added 15/04/2021) 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37073421/ results of a secondary analysis (added 26/04/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-03-31
• Study Completion: 2016-07-30
• Last Update Posted: 8 May 2023

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 1198

Inclusion Criteria

Current inclusion criteria as of 28/04/2014:
1. Capability of subject to comprehend and comply with study requirements
2. At least 18 years of age at time of consent
3. Subject is taking less than or equal to 1.1 mg of folic acid daily at the time of randomization
4. Live fetus (documented positive fetal heart prior to randomization)
5. Gestational Age between 8 0/7 and 16 6/7 weeks of pregnancy
6. Subject plans to give birth in a participating hospital site
7. Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):
7.1 Pre-existing hypertension (documented evidence of diastolic blood pressure =90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization)
7.2 Pre-pregnancy diabetes (documented evidence of Type I or Type II DM)
7.3 Twin pregnancy
7.4 Documented evidence of history of PE in a previous pregnancy
7.5 BMI > 35 kg/m2 within 3 months prior to this pregnancy or up to randomization of this pregnancy (documented evidence of height and weight to calculate BMI is required)

Inclusion criteria from 13/03/2012 to 28/04/2014:
1. Capability of subject to comprehend and comply with study requirements
2. At least 18 years of age at time of consent
3. Subject is taking less than or equal to 1.1 mg of folic acid daily at the time of randomization
4. Live fetus (documented positive fetal heart prior to randomization)
5. Gestational Age between 8 0/7 and 16 6/7 weeks of pregnancy
6. Subject plans to give birth in a participating hospital site
7. Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):
7.1 Pre-existing hypertension (documented evidence of diastolic blood pressure =90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization)
7.2 Pre-pregnancy diabetes (documented evidence of Type I or Type II DM)
7.3 Twin pregnancy
7.4 Documented evidence of history of PE in a previous pregnancy
7.5 BMI > 35 kg/m2 within 3 months prior to this pregnancy or during the first trimester of this pregnancy (documented evidence of height and weight to calculate BMI is required)

Inclusion criteria from 14/07/2011 to 13/03/2012:
1. Capability of subject to comprehend and comply with study requirements
2. At least 18 years of age at time of consent
3. Subject is taking less than or equal to 1 mg of folic acid daily at the time of randomization
4. Live fetus (documented positive fetal heart prior to randomization)
5. Gestational Age between 8 0/7 and 16 6/7 weeks of pregnancy
6. Subject plans to give birth in a participating hospital site
7. Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):
7.1 Pre-existing hypertension (documented evidence of diastolic blood pressure =90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization)
7.2 Pre-pregnancy diabetes (documented evidence of Type I or Type II DM)
7.3 Twin pregnancy
7.4 Documented evidence of history of PE in a previous pregnancy
7.5 BMI > 35 kg/m2 within 3 months pri

Exclusion Criteria

Current exclusion criteria as of 14/07/2011:
1. Known history or presence of any clinically significant disease or condition which would be a contraindication to folic acid supplementation of up to 5.1 mg daily for the duration of pregnancy
2. Known major fetal anomaly or fetal demise
3. History of medical complications, including:
3.1 Renal disease with altered renal function
3.2 Epilepsy
3.3 Cancer, or
3.4 Use of folic acid antagonists such as valproic acid
4. Individual who is currently enrolled or has participated in another clinical trial or who received an investigational drug within 3 months of the date of randomization (unless approved by the Trial Coordinating Centre)
5. Known history or presence of:
5.1 Alcohol abuse (= 2 drinks per day) or alcohol dependence
5.2 Illicit drug/substance use and/or dependence
6. Known hypersensitivity to folic acid
7. Multiple Pregnancy (triplets or more)
8. Participation in this study in a previous pregnancy

Previous exclusion criteria:
1. Known history or presence of any clinically significant disease or condition, as determine by the Principal Investigator which he/she believes would be a contraindication to folic acid supplementation of up to 5 mg daily for the pregnancy duration
2. Women who have known abnormalities (e.g. hydatidiform mole) or known foetal chromosomal or major malformations in the current pregnancy
3. Women who have a history of medical complications, including:
3.1. Untreated hypo/hyper thyroidism
3.2. Renal disease with altered renal function
3.3. Epilepsy
3.4. Any collagen disease such as lupus erythromatosus and scleroderma
3.5. Active and chronic liver disease (hepatitis)
3.6. Cancer
3.7. Use of folic acid antagonists such as valproic acid
4. Threatened abortion. Women with a previous bleeding in the first trimester, can be included if the site documents a viable foetus at the time of recruitment through ultrasound.
5. Women who are using illicit drug or alcohol abuse (greater than or equal to 2 drinks per day) during current pregnancy
6. Known history or presence of:
6.1. Alcoholism
6.2. Drug dependence and/or substance abuse
6.3. Hypersensitivity or idiosyncratic reaction to folic acid
7. Previously been enrolled in this study

Study & Design

• Study Type: Interventional
• Study Design: Not specified