Infant, NewbornPhase 1/2Vitamin ANCT01203488
Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants
A Phase 1/2 study testing Vitamin A in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 11 sites in United States.
Trial summary
This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A and determine if this would increase the rate of survival without bronchopulmonary dysplasia (BPD) and reduce the risk of sepsis. Read more about this study
- Who is it for?
- Ages 24 to 96 hours
- Conditions the study is for
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
- What is being tested?
- Vitamin A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 807 participants
- Where
- 11 sitesUnited States
- Study dates
- Jan 1996to Jul 1999
- Phase
- Phase 1/2
- 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 24 to 96 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants wtih birth weights from 401-1,000g
- Receiving mechanical ventilation or supplemental oxygen at 24-96 hours of age
Who cannot join
- Major congenital anomalies
- Congenital nonbacterial infection
- Infants diagnosed with a terminal illness (as indicated by a pH below 6.80 or by the presence of hypoxia with bradycardia for more than two hours)
- Infants who were to receive vitamin A in a parenteral fat emulsion or in doses exceeding recommendations for multivitamin preparations
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Emory University
Atlanta, Georgia, 30303
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Indiana University
Indianapolis, Indiana, 46202
University of Tennessee
Memphis, Tennessee, 38163
University of Miami
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
George Washington University
Washington D.C., District of Columbia, 20052
About this study
Official title: Randomized Trial of Vitamin A Supplementation for Extremely-Low-Birth-Weight
This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A and determine if this would increase the rate of survival without bronchopulmonary dysplasia (BPD) and reduce the risk of sepsis. Infants with birth weights from 401-1000g and who were on mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the Vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.
Read the detailed description
Infants with extremely low birth weights (≤1,000 g) have low plasma and tissue concentrations of vitamin A, and vitamin A deficiency may predispose these infants to chronic lung disease. A meta-analysis of clinical trials of vitamin A supplementation for preterm infants revealed a 17% increase in the rate of survival without chronic lung disease, which approached statistical significance.
This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A than that used in previous trials in extremely-low-birth-weight (ELBW) infants. We hypothesized that vitamin A supplementation would increase the rate of survival without bronchopulmonary dysplasia and reduce the risk of sepsis.
Infants with birth weights from 401-1000g and who received mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.
Serum vitamin A was measured in a central laboratory at base line and at 28 days in the first 300 infants. On study day 28 (two to three days after the last treatment and immediately after a blood sample was collected), the relative dose-response was evaluated.
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Bronchopulmonary Dysplasia, Respiration, Artificial
- Being tested
- Vitamin A, Sham Procedure
- Keywords
- NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Vitamin A, Chronic Lung Disease
- Medical subject headings
- Premature Birth, Bronchopulmonary Dysplasia, Respiratory Aspiration, Respiratory Distress Syndrome, Newborn, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin ADrug
5,000 IU (0.1 ml) was given on Mondays, Wednesdays, and Fridays for four weeks.
Sham ProcedureOther
Control infants received a sham procedure rather than placebo injections.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Vitamin A group. Receives: Drug: Vitamin A |
| Control | Sham comparator | Sham procedure Control group. Receives: Other: Sham Procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronic lung disease or death
Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age.
Measured: 36 weeks' postmenstrual age
Secondary outcomes (1)
Sepsis
Sepsis was defined on the basis of a positive blood culture and treatment with antibiotics for at least five days (unless the infant died within five days).
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startJan 1996
- Primary completionJul 1997
- Study completionJul 1999
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Infant, NewbornStudies 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 807 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- National Center for Research Resources (NCRR)
- Investigators
- Jon E. Tyson, MD MPH, Study director, University of Texas Southwestern Medical CenterWilliam Oh, MD, Principal investigator, Brown University, Women and Infants HospitalJoel Verter, PhD, Principal investigator, George Washington University Biostatistics CenterRichard A. Ehrenkranz, MD, Principal investigator, Yale UniversityBarbara J. Stoll, MD, Principal investigator, Emory UniversityJames A. Lemons, MD, Principal investigator, Indiana UniversityDavid K. Stevenson, MD, Principal investigator, Stanford UniversityCharles R. Bauer, MD, Study director, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01203488
- Sponsor's protocol ID
- NICHD-NRN-0015
- Other IDs
- U10HD021373, U10HD027904, U01HD019897, U10HD027871, M01RR006022, U10HD027851, U10HD027856, M01RR000750
- Acronym
- Vitamin A
- Status last verified
- Sep 2017
- First submitted
- 15 Sep 2010
- Last updated
- 26 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stark AR, Tyson JE, Hibberd PL. Variation among institutional review boards in evaluating the design of a multicenter randomized trial. J Perinatol. 2010 Mar;30(3):163-9. doi: 10.1038/jp.2009.157. Epub 2009 Oct 1.
PubMed 19798046Kennedy KA, Stoll BJ, Ehrenkranz RA, Oh W, Wright LL, Stevenson DK, Lemons JA, Sowell A, Mele L, Tyson JE, Verter J. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network. Early Hum Dev. 1997 Jul 24;49(1):19-31. doi: 10.1016/s0378-3782(97)01869-0.
PubMed 9179535Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.
PubMed 10379020Ambalavanan N, Tyson JE, Kennedy KA, Hansen NI, Vohr BR, Wright LL, Carlo WA; National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months. Pediatrics. 2005 Mar;115(3):e249-54. doi: 10.1542/peds.2004-1812. Epub 2005 Feb 15.
PubMed 15713907Rysavy MA, Li L, Tyson JE, Jensen EA, Das A, Ambalavanan N, Laughon MM, Greenberg RG, Patel RM, Pedroza C, Bell EF; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial. J Pediatr. 2021 Sep;236:78-85.e5. doi: 10.1016/j.jpeds.2021.05.022. Epub 2021 May 15.
PubMed 34004189
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Vitamin A Supplementation for Extremely-Low-Birth-Weight
- ClinicalTrials.gov ID
- NCT01203488
- Acronym / sponsor ID
- Vitamin A / NICHD-NRN-0015
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Bronchopulmonary Dysplasia, Respiration, Artificial
- Keywords
- NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Vitamin A, Chronic Lung Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 807 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Jan 1996
- Primary completion
- Jul 1997 (actual)
- Study completion
- Jul 1999 (actual)
- First posted
- 16 Sep 2010 (estimated)
- 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.
This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A and determine if this would increase the rate of survival without bronchopulmonary dysplasia (BPD) and reduce the risk of sepsis. Infants with birth weights from 401-1000g and who were on mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the Vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.
Detailed description
Infants with extremely low birth weights (≤1,000 g) have low plasma and tissue concentrations of vitamin A, and vitamin A deficiency may predispose these infants to chronic lung disease. A meta-analysis of clinical trials of vitamin A supplementation for preterm infants revealed a 17% increase in the rate of survival without chronic lung disease, which approached statistical significance.
This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A than that used in previous trials in extremely-low-birth-weight (ELBW) infants. We hypothesized that vitamin A supplementation would increase the rate of survival without bronchopulmonary dysplasia and reduce the risk of sepsis.
Infants with birth weights from 401-1000g and who received mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.
Serum vitamin A was measured in a central laboratory at base line and at 28 days in the first 300 infants. On study day 28 (two to three days after the last treatment and immediately after a blood sample was collected), the relative dose-response was evaluated.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Vitamin AVitamin A group. |
| Control | Sham comparator | Other: Sham ProcedureSham procedure Control group. |
Who may qualify
- Ages
- 24 to 96 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants wtih birth weights from 401-1,000g
- Receiving mechanical ventilation or supplemental oxygen at 24-96 hours of age
Key exclusion criteria (4 listed)
- Major congenital anomalies
- Congenital nonbacterial infection
- Infants diagnosed with a terminal illness (as indicated by a pH below 6.80 or by the presence of hypoxia with bradycardia for more than two hours)
- Infants who were to receive vitamin A in a parenteral fat emulsion or in doses exceeding recommendations for multivitamin preparations
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 |
|---|---|---|
| Vitamin A5,000 IU (0.1 ml) was given on Mondays, Wednesdays, and Fridays for four weeks. | Drug | Experimental |
| Sham ProcedureControl infants received a sham procedure rather than placebo injections. | Other | Control |
Primary outcome
Chronic lung disease or death
Time frame: 36 weeks' postmenstrual age
Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age.
1 secondary outcome
Sepsis
Time frame: 5 days
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 26 Sep 2017.
- Background: PubMed 19798046Stark AR, Tyson JE, Hibberd PL. Variation among institutional review boards in evaluating the design of a multicenter randomized trial. J Perinatol. 2010 Mar;30(3):163-9. doi: 10.1038/jp.2009.157. Epub 2009 Oct 1.
- Results publication: PubMed 9179535Kennedy KA, Stoll BJ, Ehrenkranz RA, Oh W, Wright LL, Stevenson DK, Lemons JA, Sowell A, Mele L, Tyson JE, Verter J. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network. Early Hum Dev. 1997 Jul 24;49(1):19-31. doi: 10.1016/s0378-3782(97)01869-0.
- Results publication: PubMed 10379020Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.
- Results publication: PubMed 15713907Ambalavanan N, Tyson JE, Kennedy KA, Hansen NI, Vohr BR, Wright LL, Carlo WA; National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months. Pediatrics. 2005 Mar;115(3):e249-54. doi: 10.1542/peds.2004-1812. Epub 2005 Feb 15.
- Derived from this study: PubMed 34004189Rysavy MA, Li L, Tyson JE, Jensen EA, Das A, Ambalavanan N, Laughon MM, Greenberg RG, Patel RM, Pedroza C, Bell EF; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial. J Pediatr. 2021 Sep;236:78-85.e5. doi: 10.1016/j.jpeds.2021.05.022. Epub 2021 May 15.
- NICHD Neonatal Research NetworkLink provided by the sponsor.
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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.
Jon E. Tyson, MD MPH study director
University of Texas Southwestern Medical Center
William Oh, MD principal investigator
Brown University, Women and Infants Hospital
Joel Verter, PhD principal investigator
George Washington University Biostatistics Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vitamin A in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 11 sites in United States.
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 2 inclusion and 4 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 26 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Chronic lung disease or death (time frame: 36 weeks' postmenstrual age). 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 NCT01203488, which also lists 5 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 26 Sep 2017.