Late Vitamin K Deficiency-related BleedingVKLBNCT05713045
Late Vitamin K Deficiency-related Bleeding in Neonates (VKLB): Comparison of Different Strategies to Prophylaxis
An observational study of Late Vitamin K Deficiency-related Bleeding, run by Azienda Ospedaliero-Universitaria di Parma at 1 site in Italy.
Trial summary
The goal of this multicentric observational study was to compare four vitamin K dosing regimens in exclusively breastfed healthy term newborns. The main questions it aims to answer were: comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4… Read more about this study
- Who is it for?
- Ages 1 to 1 day
- Conditions the study is for
- Late Vitamin K Deficiency-related Bleeding
- What is being tested?
- Konakion
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- 27 Mar 2020to 20 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 to 1 day
- All sexes
- Child
Study population: Term healthy newborn born from March 2019 to June 2021
Who may be able to join
- gestational age between 37+ 0/7 and 42+ 0/7 weeks
- exclusive breastfeeding
- Informed consent by at least one parent
Who cannot join
- gestational age less than 37+ 0/7 weeks or more than 42+0/7 weeks
- neonatal disease
- liver disease
- formula milk or mixed milk feeding
- withdrawal of informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Late Vitamin K Deficiency-related Bleeding in Neonates (VKDB): Comparison of Four Different Strategies to Prophylaxis Measuring Proteins Induced by Vitamin K Absence (PIVKA)
The goal of this multicentric observational study was to compare four vitamin K dosing regimens in exclusively breastfed healthy term newborns. The main questions it aims to answer were:
- comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
- to investigate the compliance and safety of oral vitamin K 1 administration Participants received vitamin K prophilaxis according to birth Hospital regimen. A blood sample was taken at 48 hours, 1 month and 3 months of life. Plasmatic PIVKA-II concentretion was be dosed
Read more
Researchers compared four groups of Vitamin K dosing regimens:
- an intramuscolar injection of 1 mg vitamin K at birth
- an intramuscolar injection of 1 mg vitamin K at birth followed by 50 μg/die orally from the second to the fourteenth week of life.
- an intramuscolar injection of 1 mg vitamin K at birth followed by 150 μg/die orally from the second to the fourteenth week of life.
- an oral dose of 2 mg vitamin K at birth, followed by a second dose at 4 weeks, and a third dose at 12 weeks to see if there is PIVKA-II plasmatic concentration differences.
Read the detailed description
Partecipanting Centers
- Azienda Ospedaliera Universitaria di Parma
- Azienda Ospedaliera Universitaria di Siena
- Ospedale Buon Consiglio Fatebenefratelli, Napoli
- Ospedale Di Venere, Bari
Materials and Methods Term healthy newborn born from March 2019 to June 2021 was enrolled Vitamin K formulation was Konakion 2 mg/0,2 ml MM paediatric, solution for injection or oral administration, Cheplapharm Arzneimittel GMBH
PIVKA level was was measured on blood drops obtained by heel prick at 48 hours of life, 1 month and 3 months, using the PIVKA-II ELISA Kit, MyBiosource, San Diego, CA, USA.
Blood samples (0,5 ml) were collected in Lithium Heparine draw. After centrifugation at 1000 rpm for 15 minutes plasma was frozen and stored at -20°C. The samples were subsequently analyzed in the Laboratorio di Patologia Clinica, Università degli Studi di Siena.
Medication adherence was measured by questionnaires administrated to parents at 1 month and 3 months of life. A protocol violation (lack of vitamin K administration, concomitant use of other drugs except vitamins, ormula milk or mixed milk feeding) led to exclution of patients
Addictional collected data were:
- sex
- gestational age
- mode of delivery
- Apgar score
- antenatal corticosteroids
- antenatal antibiotics or others drugs
- birth weight
- premature rupture of membranes
Statistical analysis:
Statistical analysis was performed using SPSS 23.0 (IBM, Chicago, IL, USA) and MATLAB 8.0 (The MathWorks, Inc., Natick, MA, USA).
Data were tested for normality with the Shapiro-Wilk test, with the results expressed as mean and standard deviation, median and interquartile range, or frequency and percentage. Data were analyzed using Student's t-test or Wilcoxon rank-sum test for continuous data, and chi-square or Fisher's exact test for categorical variables. A two-tailed p-value <0.05 was considered significant. PIVKA levels were analyzed with repeated measures-ANOVA: different administration regimen was inserted as covariate.
- Being tested
- Konakion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KonakionDietary supplement
Comparing 4 different regimen of Vitamin K administration in newborn
| Study group | Role | What they receive |
|---|---|---|
| intramuscolar injection | intramuscolar injection of 1 mg vitamin K at birth Receives: Dietary Supplement: Konakion | |
| intramuscolar injection following by oral low dose | intramuscolar injection of 1 mg vitamin K at birth followed by 50 μg/die orally from the second to the fourteenth week of life Receives: Dietary Supplement: Konakion | |
| intramuscolar injection following by oral high dose | intramuscolar injection of 1 mg vitamin K at birth followed by 150 μg/die orally from the second to the fourteenth week of life Receives: Dietary Supplement: Konakion | |
| oral administration | oral dose of 2 mg vitamin K at birth, followed by a second dose at 4 weeks, and a third dose at 12 weeks Receives: Dietary Supplement: Konakion |
What is being measured
The primary outcome is the main question the study is designed to answer.
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
PIVKA-II level measured by blood samples
Measured: 48 hours of life
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
PIVKA-II level measured by blood samples
Measured: 1 month of life
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
PIVKA-II level measured by blood samples
Measured: 3 months of life
Secondary outcomes (3)
to investigate the compliance and safety of oral vitamin K 1 administration
Medication Adherence Questionnaire
Measured: 48 hours of life
to investigate the compliance and safety of oral vitamin K 1 administration
Medication Adherence Questionnaire
Measured: 1 month of life, 3 month of life
to investigate the compliance and safety of oral vitamin K 1 administration
Medication Adherence Questionnaire
Measured: 3 months of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2023
- Study start27 Mar 2020
- Primary completion1 Oct 2021
- Study completion20 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Late Vitamin K Deficiency-related BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Parma
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Serafina Perrone, Azienda Ospedaliero-Universitaria di Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05713045
- Sponsor's protocol ID
- 12150
- Acronym
- VKLB
- Status last verified
- Feb 2023
- First submitted
- 24 Jan 2023
- Last updated
- 6 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lembo C, Buonocore G, Perrone S. The challenge to define the optimal prophylactic regimen for vitamin K deficiency bleeding in infants. Acta Paediatr. 2021 Apr;110(4):1113-1118. doi: 10.1111/apa.15566. Epub 2020 Oct 6.
PubMed 32892390Shearer MJ. Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev. 2009 Mar;23(2):49-59. doi: 10.1016/j.blre.2008.06.001. Epub 2008 Sep 19.
PubMed 18804903American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003 Jul;112(1 Pt 1):191-2.
PubMed 12837888Mihatsch WA, Braegger C, Bronsky J, Campoy C, Domellof M, Fewtrell M, Mis NF, Hojsak I, Hulst J, Indrio F, Lapillonne A, Mlgaard C, Embleton N, van Goudoever J; ESPGHAN Committee on Nutrition. Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2016 Jul;63(1):123-9. doi: 10.1097/MPG.0000000000001232.
PubMed 27050049
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Late Vitamin K Deficiency-related Bleeding in Neonates (VKDB): Comparison of Four Different Strategies to Prophylaxis Measuring Proteins Induced by Vitamin K Absence (PIVKA)
- ClinicalTrials.gov ID
- NCT05713045
- Acronym / sponsor ID
- VKLB / 12150
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ParmaUniversity, hospital or other
- Study start
- 27 Mar 2020 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 20 Jan 2023 (actual)
- First posted
- 6 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this multicentric observational study was to compare four vitamin K dosing regimens in exclusively breastfed healthy term newborns. The main questions it aims to answer were:
- comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
- to investigate the compliance and safety of oral vitamin K 1 administration Participants received vitamin K prophilaxis according to birth Hospital regimen. A blood sample was taken at 48 hours, 1 month and 3 months of life. Plasmatic PIVKA-II concentretion was be dosed
Researchers compared four groups of Vitamin K dosing regimens:
- an intramuscolar injection of 1 mg vitamin K at birth
- an intramuscolar injection of 1 mg vitamin K at birth followed by 50 μg/die orally from the second to the fourteenth week of life.
- an intramuscolar injection of 1 mg vitamin K at birth followed by 150 μg/die orally from the second to the fourteenth week of life.
- an oral dose of 2 mg vitamin K at birth, followed by a second dose at 4 weeks, and a third dose at 12 weeks to see if there is PIVKA-II plasmatic concentration differences.
Detailed description
Partecipanting Centers
- Azienda Ospedaliera Universitaria di Parma
- Azienda Ospedaliera Universitaria di Siena
- Ospedale Buon Consiglio Fatebenefratelli, Napoli
- Ospedale Di Venere, Bari
Materials and Methods Term healthy newborn born from March 2019 to June 2021 was enrolled Vitamin K formulation was Konakion 2 mg/0,2 ml MM paediatric, solution for injection or oral administration, Cheplapharm Arzneimittel GMBH
PIVKA level was was measured on blood drops obtained by heel prick at 48 hours of life, 1 month and 3 months, using the PIVKA-II ELISA Kit, MyBiosource, San Diego, CA, USA.
Blood samples (0,5 ml) were collected in Lithium Heparine draw. After centrifugation at 1000 rpm for 15 minutes plasma was frozen and stored at -20°C. The samples were subsequently analyzed in the Laboratorio di Patologia Clinica, Università degli Studi di Siena.
Medication adherence was measured by questionnaires administrated to parents at 1 month and 3 months of life. A protocol violation (lack of vitamin K administration, concomitant use of other drugs except vitamins, ormula milk or mixed milk feeding) led to exclution of patients
Addictional collected data were:
- sex
- gestational age
- mode of delivery
- Apgar score
- antenatal corticosteroids
- antenatal antibiotics or others drugs
- birth weight
- premature rupture of membranes
Statistical analysis:
Statistical analysis was performed using SPSS 23.0 (IBM, Chicago, IL, USA) and MATLAB 8.0 (The MathWorks, Inc., Natick, MA, USA).
Data were tested for normality with the Shapiro-Wilk test, with the results expressed as mean and standard deviation, median and interquartile range, or frequency and percentage. Data were analyzed using Student's t-test or Wilcoxon rank-sum test for continuous data, and chi-square or Fisher's exact test for categorical variables. A two-tailed p-value <0.05 was considered significant. PIVKA levels were analyzed with repeated measures-ANOVA: different administration regimen was inserted as covariate.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| intramuscolar injection | – | Dietary Supplement: Konakionintramuscolar injection of 1 mg vitamin K at birth |
| intramuscolar injection following by oral low dose | – | Dietary Supplement: Konakionintramuscolar injection of 1 mg vitamin K at birth followed by 50 μg/die orally from the second to the fourteenth week of life |
| intramuscolar injection following by oral high dose | – | Dietary Supplement: Konakionintramuscolar injection of 1 mg vitamin K at birth followed by 150 μg/die orally from the second to the fourteenth week of life |
| oral administration | – | Dietary Supplement: Konakionoral dose of 2 mg vitamin K at birth, followed by a second dose at 4 weeks, and a third dose at 12 weeks |
Who may qualify
- Ages
- 1 to 1 day
- Sex
- All
- Age groups
- Child
- Study population
- Term healthy newborn born from March 2019 to June 2021
Key inclusion criteria (3 listed)
- gestational age between 37+ 0/7 and 42+ 0/7 weeks
- exclusive breastfeeding
- Informed consent by at least one parent
Key exclusion criteria (5 listed)
- gestational age less than 37+ 0/7 weeks or more than 42+0/7 weeks
- neonatal disease
- liver disease
- formula milk or mixed milk feeding
- withdrawal of informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KonakionComparing 4 different regimen of Vitamin K administration in newborn | Dietary supplement | intramuscolar injection, intramuscolar injection following by oral high dose, intramuscolar injection following by oral low dose, oral administration |
Primary outcome
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
Time frame: 48 hours of life
PIVKA-II level measured by blood samples
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
Time frame: 1 month of life
PIVKA-II level measured by blood samples
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
Time frame: 3 months of life
PIVKA-II level measured by blood samples
3 secondary outcomes
to investigate the compliance and safety of oral vitamin K 1 administration
Time frame: 48 hours of life
to investigate the compliance and safety of oral vitamin K 1 administration
Time frame: 1 month of life, 3 month of life
to investigate the compliance and safety of oral vitamin K 1 administration
Time frame: 3 months of life
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Background: PubMed 32892390Lembo C, Buonocore G, Perrone S. The challenge to define the optimal prophylactic regimen for vitamin K deficiency bleeding in infants. Acta Paediatr. 2021 Apr;110(4):1113-1118. doi: 10.1111/apa.15566. Epub 2020 Oct 6.
- Background: PubMed 18804903Shearer MJ. Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev. 2009 Mar;23(2):49-59. doi: 10.1016/j.blre.2008.06.001. Epub 2008 Sep 19.
- Background: PubMed 12837888American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003 Jul;112(1 Pt 1):191-2.
- Background: PubMed 27050049Mihatsch WA, Braegger C, Bronsky J, Campoy C, Domellof M, Fewtrell M, Mis NF, Hojsak I, Hulst J, Indrio F, Lapillonne A, Mlgaard C, Embleton N, van Goudoever J; ESPGHAN Committee on Nutrition. Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2016 Jul;63(1):123-9. doi: 10.1097/MPG.0000000000001232.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Late Vitamin K Deficiency-related Bleeding, run by Azienda Ospedaliero-Universitaria di Parma at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months (time frame: 48 hours of life). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05713045, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.