NCT07620236

Brief Summary

The OK Daily Study is a multi-centred, part-randomised, part blinded, four cohort study. We are exploring daily dietary supplementation with vitamin K2, specifically menaquinone-7 (MK-7), given to breastfed infants or breastfeeding mothers to see whether this improves the incidence of biochemical vitamin K deficiency in the infants at 2 months postnatal age. The overall aims are:

  • To compare infant MK-7 supplementation with placebo
  • To compare maternal MK-7 supplementation with placebo
  • To compare infant MK-7 supplementation and maternal MK-7 supplementation
  • To compare infant MK-7 supplementation with vitamin K1 supplementation via infant formula milk. Once recruited, mother and infant pairs will be grouped initially based on the families' feeding choice. Breastfed infants will then be randomised 2:1 to the infant supplementation or maternal supplementation group. Within the infant supplementation group, infants will either receive MK-7 with vitamin D or a placebo containing vitamin D. Follow up will occur at 2 months postnatal age (range 2-3 months postnatal age), where bloods and breastmilk samples will be collected to assess the infant and maternal vitamin K status.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
134

participants targeted

Target at P50-P75 for not_applicable

Timeline
24mo left

Started Aug 2026

Typical duration for not_applicable

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 13, 2026

Completed
20 days until next milestone

First Posted

Study publicly available on registry

June 2, 2026

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2026

Expected
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2027

11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2028

Last Updated

June 2, 2026

Status Verified

May 1, 2026

Enrollment Period

1.1 years

First QC Date

May 13, 2026

Last Update Submit

May 27, 2026

Conditions

Infant Vitamin K StatusVitamin K Deficiency Bleeding

Keywords

Oral vitamin Kvitamin K1 vs K2menaquinone-7 (MK-7)vitamin K statusPIVKA-IIundercarboxylated/carboxylated osteocalcin rationeonateinfantbreastfeeding

Outcome Measures

Primary Outcomes (1)

  • Comparison of the proportion of participants who have a PIVKA-II >0.05 AU/mL in the unsupplemented and supplemented infants.

    PIVKA-II = protein induced by vitamin K antagonism/absence; clotting protein II. Measured via serum blood sample in arbitrary units/mL. For the primary outcome, this is the comparison between the supplemented and unsupplemented infants.

    2 months postnatal age (range 2-3 months).

Secondary Outcomes (8)

  • Comparison of the proportion of participants who have a PIVKA-II >0.05 AU/mL in the various study groups.

    2 months postnatal age (range 2-3 months).

  • Comparison of serum levels of osteocalcin (undercarboxylated and carboxylated) between the study groups.

    2 months postnatal age (range 2-3 months).

  • Comparison of the percentage of undercarboxylated osteocalcin as a proportion of total osteocalcin (%GluOC) between the study groups.

    2 months postnatal age (range 2-3 months).

  • Comparison of serum levels of dephosphorylated undercarboxylated matrix Gla Protein in included participants between the study groups.

    2 months postnatal age (range 2-3 months).

  • Comparison of levels of serum K vitamers (including, but no limited to, vitamin K1 and menaquinone-7) between the study groups.

    2 months postnatal age (range 2-3 months).

  • +3 more secondary outcomes

Study Arms (2)

Mother and infant pairs who are breastfeeding.

OTHER

Group 1 = infant supplementation group. Infants in this group will be randomised to receive either 6 drops a day containing 45 micrograms/day of MK-7 plus 10 micrograms/day vitamin D3 OR 10 micrograms/day vitamin D3 only (the active placebo, containing no vitamin K) Group 2 = maternal supplementation group. Mothers in this group will be given 2 mg/day MK-7 capsules. Infants in this group will receive 10 micrograms/day vitamin D3.

Other: Combined MK-7 + vitamin D3 dropsOther: Vitamin D3 DropsOther: MK-7 capsules

Formula Feeding Infants

ACTIVE COMPARATOR

Infants who are exclusively formula feeding. These infants will receive the recommended daily amount of vitamin K through their formula milk intake and so will not receive any additional vitamin K supplementation.

Other: Vitamin D3 Drops

Interventions

Combined MK-7 + vitamin D3 dropsOTHER

6 drops/day providing 45 micrograms/day MK-7 plus 10 micrograms/day of vitamin D3

Also known as: Vitamin K2 supplemented infant group
Mother and infant pairs who are breastfeeding.
Vitamin D3 DropsOTHER

6 drops/day providing 10 micrograms/day vitamin D3 and no supplementary MK-7.

Also known as: Vitamin K2 unsupplemented group
Formula Feeding InfantsMother and infant pairs who are breastfeeding.
MK-7 capsulesOTHER

1 mg capsules of menaquinone-7, with a daily dose of 2 mg (i.e. 2 capsules per day)

Mother and infant pairs who are breastfeeding.

Eligibility Criteria

AgeUp to 7 Days
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Infants, and mothers of infants, born ≥37 weeks gestational age
  • Standard dose of intramuscular (IM) vitamin K prophylaxis given to the neonate following birth
  • For breastfeeding mothers: the mother intends to exclusively/predominantly breastfeed their baby for at least 2 months

You may not qualify if:

  • Inability or refusal to provide informed consent
  • Inability to adhere to or comply with study procedures
  • IM vitamin K prophylaxis not received at birth (parents declined vitamin K prophylaxis or parents chose for neonate to receive an oral course of vitamin K prophylaxis instead)
  • Evidence of conjugated hyperbilirubinaemia (these babies are at higher risk of VKDB)
  • Mothers, and babies born to mothers, who are taking any medication that could affect or antagonise vitamin K metabolism (i.e. warfarin, the anti-epileptic drugs phenytoin or carbamazepine, and cephalosporin, rifampicin and isoniazid antimicrobials)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (5)

  • Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83. doi: 10.1182/blood-2006-08-040709. Epub 2006 Dec 7.

    PMID: 17158229BACKGROUND

  • Perrone S, De Bernardo G, Lembo C, Dell'Orto V, Giordano M, Beretta V, Petrolini C, Gambini L, Toni AL, Parigi G, Fontanarosa I, Natale MP, D'Amato G, Sordino D, Buonocore G. Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study. Eur J Clin Invest. 2024 Apr;54(4):e14141. doi: 10.1111/eci.14141. Epub 2023 Dec 9.

    PMID: 38071415BACKGROUND

  • Clarke P, Shearer MJ, Card DJ, Nichols A, Ponnusamy V, Mahaveer A, Voong K, Dockery K, Holland N, Mulla S, Hall LJ, Maassen C, Lux P, Schurgers LJ, Harrington DJ. Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth. J Thromb Haemost. 2022 Dec;20(12):2773-2785. doi: 10.1111/jth.15874. Epub 2022 Oct 3.

    PMID: 36087073BACKGROUND

  • Clarke P, Mitchell SJ, Shearer MJ. Total and Differential Phylloquinone (Vitamin K1) Intakes of Preterm Infants from All Sources during the Neonatal Period. Nutrients. 2015 Sep 25;7(10):8308-20. doi: 10.3390/nu7105393.

    PMID: 26426042BACKGROUND

  • Clarke P, Embleton ND, Fewtrell M, Harrington DJ, Kelly AM, Moris N, Patto A, Ponnusamy V, Vasu V, Shearer MJ. Vitamin K: missed at peril-the case for extra supplementation to prevent deficiency in breastfed preterm infants. Arch Dis Child Fetal Neonatal Ed. 2024 Oct 18;109(6):679-680. doi: 10.1136/archdischild-2023-326737. No abstract available.

    PMID: 38429074BACKGROUND

MeSH Terms

Conditions

Vitamin K Deficiency BleedingBreast Feeding

Condition Hierarchy (Ancestors)

Vitamin K DeficiencyBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant Nutrition DisordersNutrition DisordersNutritional and Metabolic DiseasesAvitaminosisDeficiency DiseasesMalnutritionFeeding BehaviorBehavior

Study Officials

  • Paul Clarke, Professor

    Norfolk and Norwich University Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Professor Clarke

CONTACT

01603 286286PAUL.CLARKE@nnuh.nhs.uk

Carianne Dr Lewis

CONTACT

Carianne.Lewis@nnuh.nhs.uk

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Masking Details
Group 1 is double blinded. Groups 2 and 3 are open label by their nature.
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 13, 2026

First Posted

June 2, 2026

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

August 1, 2028

Last Updated

June 2, 2026

Record last verified: 2026-05