Clinical Trials Register

Summary
EudraCT Number:	2012-001918-42
Sponsor's Protocol Code Number:	2009-107(Canadian)
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-07-30
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-001918-42

A.3

Full title of the trial

Effect of folic acid supplementation in pregnancy on preeclampsia - Folic Acid Clinical Trial (FACT)
A randomized, double-blind, placebo-controlled, Phase III, international multi-centre study of 4.0 mg of Folic Acid supplementation in pregnancy for the prevention of preeclampsia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Effect of Folic Acid supplementation in pregnancy on preeclampsia

A.3.2

Name or abbreviated title of the trial where available

Folic Acid Clinical Trial (FACT)

A.4.1

Sponsor's protocol code number

2009-107(Canadian)

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN23781770

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01355159

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Ottawa Hospital Research Institute
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Canadian Institute of Health Research
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ottawa Hospital Research Institute
B.5.2	Functional name of contact point	Marissa Akow
B.5.3	Address:
B.5.3.1	Street Address	Ottawa Hospital Research Institute, 725 Parkdale Avenue
B.5.3.2	Town/ city	Ottawa, ON
B.5.3.3	Post code	K1Y 4E9
B.5.3.4	Country	Canada
B.5.4	Telephone number	613-737-8899 ext 78462
B.5.5	Fax number	613-761-4920
B.5.6	E-mail	makow@ohri.ca

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Folic acid tablets
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Folic acid tablets
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Folic Acid
D.3.9.1	CAS number	59-30-3
D.3.9.3	Other descriptive name	(2S)-2-[[4-[[(2-Amino-4-oxo-1,4-dihydropteridin-6-yl) methyl]amino]benzoyl]amino]pentanedioic acid
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

pre-eclampsia

E.1.1.1

Medical condition in easily understood language

High blood pressure and protein in urine in pregnancy

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10036485
E.1.2	Term	Pre-eclampsia
E.1.2	System Organ Class	10036585 - Pregnancy, puerperium and perinatal conditions

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To ascertain if a 4mg supplementation of Folic acid taken from early pregnancy until delivery prevents preeclampsia when compared with a placebo.

E.2.2

Secondary objectives of the trial

To evaluate if the effect of folic acid on preeclampsia differs according to the following: -
a) Stage of pregnancy at intervention (8-13 and 14-16 weeks of gestation)
b) smoking
c) age
d) dietary and commercial folic acid consumption at the time of randomisation
e) subject compliance (percent of tablets used)
f) by country

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The patient has the mental capacity to understand the trial procedures and to be recruited into the the trial.

18 years or older at the time of consent

Patient is taking less than or equal to 1.1 mg of folic acid daily at the time of randomisation.

Live fetus(documented positive fetal heart beat) prior to randomisation

Gestational Age between 8 0/7 and 16 6/7 at time of randomisation.

Subject plans to give birth in the participating hospital site.

Patient must fulfil at least one of the following risk factors for Preeclampsia;
Pre-existing hypertension
Pre-pregnancy diabetes
Twin pregnancy
Documented evidence of history of PE in a previous pregnancy
BMI ≥ 35 kg/m2 within 3 months prior to this pregnancy or during 1st trimester.

E.4

Principal exclusion criteria

Indication for high dose folic acid (5 mg) during pregnancy e.g. to reduce risk of fetal central nervous system anomaly (e.g. neural tube defect) based on family or personal history.

Known history or presence of any clinically significant disease or condition which would be a contraindicaiton to folic acid supplemenation of up to 5.1 mg daily for the duration of the pregnancy.
Known major fetal anomaly or fetal demise
History of medical complications, including: -
a) renal disease with altered renal function
b) epilepsy
c) cancer
d) user of folic acid antagonists such as valproic acid

Patient who is taking part in another clinical trial, or has participated in another clinical trial, or received investigational drug within 3 months of the date of randomisation (unless approved by the Trial Coordinating Centre)

Known presence of alcohol abuse or alcohol dependance.
Drug substance use and/or dependance.

Known hypersensitivity to folic acid.
Multiple Pregnancy (triplets or more)
Participation in this study in a previous pregnancy.

E.5 End points

E.5.1

Primary end point(s)

Preeclampsia is the primary outcome measure.
PE is defined as diastolic blood pressure >/= 90 mmHg on two occasions more than 4 hours apart and proteinuria (>/= 300 mg protein/day or >/=2+ on urinalysis)in women greater than 20 weeks of gestation
Or
HELLP Haemolysis, Elevated, Liver Enzymes, Low Platelets) syndrome
Haemolysis (charateristic peripheral blood smear)
Serum LDH greater or equal to 600 U/L
Serum AST greater or equal to 70U/L
Platelet cound < 100 x 109/L
or
Superimposed pre-eclampsia, defined as history - existing hypertension (diagnosed pre pregnancy or before 20 weeks gestation) with proteinuria.

E.5.1.1

Timepoint(s) of evaluation of this end point

At delivery

E.5.2

Secondary end point(s)

Secondary outcomes will include:
Maternal death,
Severe PE (PE with convulsion or HELLP or delivery <34 weeks),
Placenta Abruption
Preterm delivery,
Premature rupture of membranes,
Antenatal inpatient length of stay,
Intrauterine growth restriction,
Spontaneous abortion,
Perinatal mortality,
Stillbirth
Neonatal death
Neonatal morbidity such as:
Retinopathy of prematurity,
Periventricular leukomalacia,
Early onset sepsis,
Necrotising enterocolitis,
Intraventricular haemorrhage,
Ventilation,
Need for O2 at 28 days,
Length of stay in Neonatal Intensive Care Unit.

E.5.2.1

Timepoint(s) of evaluation of this end point

At delivery or subsequent 6 week post partum follow up.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Information not present in EudraCT

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Canada

Chile

Netherlands

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the trial will be the LVLS.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1