The OK Daily Study

Norfolk and Norwich University Hospitals NHS Foundation Trust

Status: Begins enrollment in 1 month

Conditions: Infant Vitamin K Status; Vitamin K Deficiency Bleeding

Treatments: Other: Combined MK-7 + vitamin D3 drops; Other: MK-7 capsules; Other: Vitamin D3 Drops

Study type: Interventional

Funder types: Other

Identifiers

NCT07620236

150-12-25

Details and patient eligibility

About

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.

Full description

The OK Daily Study is a multi-centre study taking place in the Norfolk and Norwich University Hospital, Norwich, UK, and Ashford and St Peters' Hospital, Chertsey, UK.

Infants born at ≥37 weeks' gestation will be recruited in the participating site if they meet eligibility criteria and are born within the recruitment window. Recruitment will take place before the mother and infant are discharged from the hospital following birth.

The two main arms of this study are breastfeeding and formula feeding. Mother and infant pairs will initially be allocated based on the family's feeding preferences.

Infants in the breastfeeding arm will be randomised into group 1 or group 2 in a 2:1 ratio. Group 1 allocation will be blinded; group 2 allocation will be open label.

• Group 1 - infant supplementation group. Infants will receive either 45 micrograms/day of MK-7 with 10 micrograms/day vitamin D3 or a placebo consisting of 10 micrograms/day vitamin D3
• Group 2 - maternal supplementation group. Mothers in this group will receive 2 mg/day MK-7. All breastfeeding infants in this group will receive 10 micrograms/day of vitamin D3.

Formula fed infants will be in group 3 and will not require any additional supplementation as part of this study. This is because infant formula is already supplemented with adequate amounts of vitamin K1 and vitamin D.

All supplements will be started within 7 days of birth. Vitamin D drops are included for breastfed infants as per national UK guidelines.

Follow up will be as follows:

• 1 month postnatal visit (range 1-1.5 months) - phone call.

  o Confirmation of eligibility to continue, assessment of compliance with the intervention, and to schedule the in person follow up visit

• 2 months postnatal (range 2-3 months) - in person visit.

  • All babies will have a single blood sample taken.
  • Mothers who are in group 2 (mothers who have had MK-7 supplementation) and a selection of mothers from group 1 (breastfeeding mothers who are not supplemented with MK-7) will have a single blood sample taken and will be asked to provide a single breastmilk sample
  • Mothers will be asked about their opinions on practising the supplementation.

Blood samples will be analysed for vitamin K status, including Proteins Induced by Vitamin K Absence/antagonism of prothrombin (PIVKA-II) and of osteocalcin (undercarboxylated osteocalcin), dephosphorylated-undercarboxylated matrix gla-protein (dp-ucMGP) and serum vitamin K concentrations (including of vitamin K1 and MK-7). Breastmilk samples will be analysed for vitamin K concentrations (including vitamin K1 and MK-7)

Once this in person follow up visit has been completed, the mother and baby pair will have completed the study.

Enrollment: 134 estimated patients

Sex: All

Ages: Under 7 days old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• Inability or refusal to provide informed consent
• Inability to adhere to or comply with study procedures
• Babies who meet the inclusion gestation but would otherwise, as part of routine neonatal care, be provided with daily vitamin K drops (i.e. NeoKay drops) at discharge
• 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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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134 participants in 2 patient groups

Mother and infant pairs who are breastfeeding.

Other group

Description:

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.

Treatment:

Other: Vitamin D3 Drops

Other: MK-7 capsules

Other: Combined MK-7 + vitamin D3 drops

Formula Feeding Infants

Active Comparator group

Description:

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.

Treatment:

Other: Vitamin D3 Drops