Improving Multivitamin Supplementation to Pregnant Women

The purpose of this study is to compare the tolerability of Pregvit® to a common prenatal vitamin (Orifer® F) among pregnant women with morning sickness or those suffering from a variety of conditions.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting; Pregnancy; Hyperemesis Gravidarum; Morning Sickness
• Intervention / Treatment: Drug: Pregvit®; Drug: Orifer F®

Detailed Description

Presently, there is a large choice of perinatal vitamins on the market. Materna® is taken by 70% of Canadian women. A recent study by the investigators team has shown that up to 35%-53% of women with moderate to severe morning sickness discontinue their Materna®. One main reason is that its large size causes difficulties in swallowing, which prompts women to stop taking the drug. The second main reason for stopping is gastrointestinal adverse effects from the iron content, which causes nausea, vomiting and constipation.

A new periconceptional multivitamin supplement, Pregvit®, was introduced to the market in September 2003 by the Canadian company Duchesnay Inc. with the aim of trying to overcome the disadvantages of the existing multivitamin supplements. PregVit® is a prenatal multivitamin that contains 35 mg elemental iron, as ferrous fumarate. It is formulated into 2 small tablets (each tablet:16 mm × 9 mm × 4 mm), containing different vitamins and minerals, particularly separating the iron (morning tablet) from the calcium (evening tablet) to optimize iron absorption. The use of PregVit® requires a physician's prescription.

Since Materna® or other generic products are the most commonly used non-prescription (i.e. over-the-counter) prenatal multivitamins, they were not selected for comparison in the study because enrolled subjects who had discontinued a prenatal multivitamin most likely had discontinued any one of them. Ethically, subjects in this situation cannot be randomized to resume Materna® or another generic prenatal multivitamin.

Instead, Orifer F® was selected as the small-tablet prenatal multivitamin (one tablet: 5 mm radius, 5 mm thickness), containing a high iron content (60 mg elemental iron as ferrous sulphate). It is taken daily as a single tablet and the use of Orifer F® does not require a physician prescription (i.e. over-the-counter).

Comparing tolerability of PregVit® to Orifer F® would address separation of the potential effect of iron content from that of tablet size on multivitamin tolerability among pregnant women and women suffering from morning sickness or those suffering from a variety of conditions such as, Crohn's Disease, Ulcerative Colitis, Peptic-Duodenal Ulcer, Irritable Bowel Syndrome, Celiac Disease, as well as anemia or hypothyroidism.

• Study Type: Interventional
• Enrollment (Actual): 1370
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Any woman who discontinued her standard vitamins due to gastrointestinal symptoms or due to the tablet size, with one ofthe following conditions:

• Morning sickness.
• Gastrointestinal disorders: Crohn's disease, ulcerative colitis, peptic or duodenal ulcer, irritable colon, celiac disease.
• Iron deficiency anemia.
• Hypothyroidism.
• Depression.

Exclusion Criteria:

• Women who do not agree to consent to this protocol.
• Women with a known hypersensitivity to any of the ingredients of Pregvit®, or Orifer® F.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PregVit®; Women will be randomized to the '35 mg' group, who will start supplementation with PregVit® (low iron content, small size)	Drug: Pregvit®; Women were randomized to one of two groups. An information package was mailed to each woman, instructing her to commence supplementation with her assigned prenatal multivitamin, according to the product's standard dosing -twice daily for '35 mg' group; Other Names: Dietary supplement-prenatal multivitamin
Active Comparator: Orifer F®; Women will be randomized to the '60 mg' group, who will start supplementation with Orifer F® (high iron content, small size).	Drug: Orifer F®; Women were randomized to one of two groups. An information package was mailed to each woman, instructing her to commence supplementation with her assigned prenatal multivitamin, according to the product's standard dosing-once daily for '60 mg' group; Other Names: Dietary supplement-prenatal multivitamin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in rates of ability to take multivitamin [either Pregvit® or Orifer®F]	Rates of adherence and adverse events will be compared by using chi-squared tests, as appropriate. Adherence will be also compared between the 2 treatment groups through Kaplan-Meier survival curves in 2 ways. The first survival curve analysis will compare the proportion of women with standard adherence (i.e. at least 80% pill intake over time), after having commenced supplementation with the assigned multivitamin, and the p-value was determined by the Wilcoxon (Peto-Prentice) test.	Study completion was defined as completing monthly telephone interviews (when possible) to document pill intake and adverse events up until the end of pregnancy (i.e. 36 weeks gestation or further).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall use of Pregvit® vs Orifer®F (adherence)	Rates of adherence and adverse events will be compared by using chi-squared tests, as appropriate. Adherence will be also compared between the 2 treatment groups through Kaplan-Meier survival curves in 2 ways. The second survival curve analysis will compare overall adherence among women who commenced supplementation with the assigned multivitamin, at any percentage of pill intake over time, and the p-value was determined by the log rank statistic. All curves will be plotted from the coordinates of 100% (y-axis point of 1.0) at time zero (x-axis point of 0) to represent that at the beginning of the study, all subjects who commenced supplementation in each multivitamin group were adherent.	Study completion was defined as completing monthly telephone interviews (when possible) to document pill intake and adverse events up until the end of pregnancy (i.e. 36 weeks gestation or further).
The rates of overall adverse events and specific side effects between the two groups	Rates of adherence and adverse events will be compared by using chi-squared tests, as appropriate.	Study completion was defined as completing monthly telephone interviews (when possible) to document pill intake and adverse events up until the end of pregnancy (i.e. 36 weeks gestation or further).

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Duchesnay Inc.
• Investigators: Principal Investigator: Gideon Koren, MD, The Hospital for Sick Children, Toronto Canada

Publications and helpful links

Helpful Links

• Effect of iron content on the tolerability of prenatal multivitamins in pregnancy
• Adherence and tolerability of iron-containing prenatal multivitamins in pregnant women with pre-existing gastrointestinal conditions.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 24, 2014

Study Record Updates

• Last Update Posted (Estimate): November 24, 2014
• Last Update Submitted That Met QC Criteria: November 21, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Pregnancy; nausea and vomiting; Morning Sickness; hyperemesis gravidarum; perinatal vitamins
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Pregnancy Complications; Nausea; Vomiting; Hyperemesis Gravidarum; Morning Sickness
• Other Study ID Numbers: 1000005135