Early Versus Late Caffeine for ELBW Newborns

Brief Title

Early Versus Late Caffeine for ELBW Newborns

Official Title

A Randomized Double Blind Controlled Trial of Early Versus Late Caffeine for Extremely Low Birth Weight Newborns

Brief Summary

      Caffeine is routinely used in the management of apnea of prematurity. Extremely low birth
      weight (ELBW) infants are at higher risk of mortality and various neonatal morbidities such
      as bronchopulmonary dysplasia (BPD) for which caffeine has been shown to be beneficial in
      very low birth weight (VLBW) infants. The investigators' previous unpublished retrospective
      studies and recently published retrospective studies demonstrated that early caffeine given
      within 48 hours of age tended to decrease the incidence of death and BPD in ELBW newborns.
      Retrospective design can be biased as newborns with mild lung disease may have received
      caffeine early for extubation. There are several studies on pharmacodynamics and
      pharmacokinetics of caffeine. The data regarding cumulative dosage of caffeine, caffeine
      levels and BPD outcome is deficient.

      Primary objective of this study is to test the hypothesis that early caffeine given within 24
      hours of life will decrease incidence of mortality and BPD in ventilated ELBW newborns.

      This study will also test an additional hypothesis that higher caffeine dosage and caffeine
      levels are associated with decreased mortality and postnatal morbidities in studied newborns.
    

Detailed Description

      Parents will be approached either prenatally for an impending delivery of ELBW newborn or
      within 16 hours of birth. 90 newborns will be randomized to receive early caffeine within 24
      hours of life (the "study drug") and 90 newborns will receive a placebo. Either the early
      caffeine (the "study drug") or placebo will be continued throughout the first 15 days of
      life. Newborns in the early caffeine group will receive an IV bolus of 20mg/kg followed by IV
      or PO 5mg/kg daily for 14 days. The clinical team can choose to give PO caffeine if the
      newborn tolerates >75% of fluid goals by feeds. The clinical and research teams will be
      blinded; neither will know whether the newborn is receiving early caffeine or placebo. The
      clinical team will be allowed to use open labeled caffeine as deemed medically necessary
      after 24 hours of receiving either the early caffeine or placebo. Often this clinical need
      would be at the time of extubation (peri-extubation) and comprises the "late" caffeine group,
      which is also the placebo group. Perinatal and postnatal clinical characteristics will be
      prospectively collected. Clinical team may choose to hold study drug if newborns are placed
      on high frequency ventilation or if they need sedation drips for surgical procedures. Two
      blood samples will be collected one at day 7 and one at day 14 for caffeine levels. Data
      safety monitoring committee will be review mortality and morbidity in each group on a
      quarterly basis or after recruitment of every 30 newborns whichever happens earlier.
    

Study Type

Interventional

Primary Outcome

Cumulative incidence of death and bronchopulmonary dysplasia

Condition

Bronchopulmonary Dysplasia

Intervention

Caffeine

Study Arms / Comparison Groups

 Early caffeine group

Description:  90 newborns will be randomized to receive caffeine within 24 hours of life. They will receive 20mg/kg IV bolus followed by IV or PO 5mg/kg daily for the next 14 days. The clinical team may decide to give PO caffeine if the newborn tolerates >75% of fluid goals by feeds.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

220

Start Date

September 2015

Primary Completion Date

December 2018

Eligibility Criteria

        Inclusion Criteria:

          -  newborns with birth weight less than or equal to 1000grams and less than 28 weeks of
             gestation are included if intubated by 12 hours of life

        Exclusion Criteria:

          -  newborns with known congenital malformation

          -  newborns whose parents refuse consent for the study

          -  newborns who are on high frequency ventilation and/or receiving more than 80% oxygen
             at 12 hours of age

          -  newborns deemed non-viable by the clinical team (defined as those neonates born at <24
             weeks gestation and whose parents are offered withdrawal of support or do not
             resuscitate by clinical team for severity of cardiorespiratory illness at or before 12
             hours of age)

          -  newborns diagnosed with congenital heart disease within the first 12 hours of life
             (presence of a ventricular septum defect and a patent ductus arteriosus is not an
             exclusion criteria)
      

Gender

All

Ages

N/A - 4 Weeks

Accepts Healthy Volunteers

No

Contacts

Nitin S Chouthai, MD, 3137455638, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT02524249

Organization ID

1506014098

Responsible Party

Principal Investigator

Study Sponsor

Wayne State University

Collaborators

 The Gerber Foundation

Study Sponsor

Nitin S Chouthai, MD, Principal Investigator, Division of Neonatology, Department of Pediatrics, Wayne State University

Verification Date

November 2015