Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

MRI and Neurodevelopment in Preterm Infants Following Administration of High-Dose Caffeine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00809055
Recruitment Status : Completed
First Posted : December 16, 2008
Results First Posted : February 24, 2016
Last Update Posted : February 24, 2016
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Apnea of Prematurity
Intraventricular Hemorrhage
Brain Injury
Intervention Drug: Caffeine citrate
Enrollment 74
Recruitment Details  
Pre-assignment Details  
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Period Title: Overall Study
Started 37 37
Completed 28 30
Not Completed 9 7
Arm/Group Title High Dose Caffeine Standard Dose Caffeine Total
Hide Arm/Group Description

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Total of all reporting groups
Overall Number of Baseline Participants 37 37 74
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 37 participants 37 participants 74 participants
26.3  (1.9) 26.8  (1.8) 26.7  (1.8)
[1]
Measure Description: Reported as weeks of gestational age at birth
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
Female
18
  48.6%
13
  35.1%
31
  41.9%
Male
19
  51.4%
24
  64.9%
43
  58.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   5.4%
2
   5.4%
4
   5.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
18
  48.6%
23
  62.2%
41
  55.4%
White
17
  45.9%
12
  32.4%
29
  39.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 37 participants 37 participants 74 participants
37 37 74
1.Primary Outcome
Title White Matter Microstructural Maturation
Hide Description Apparent diffusion coefficient is a measure of microstructural maturation obtained from brain MRI.
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
12 patients excluded from high-dose group (7 died, 2 withdrew, 3 insufficient image quality). 10 patients excluded from standard-dose group (5 died, 1 transferred, 1 parent refused MRI, 3 insufficient image quality).
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 25 27
Mean (Standard Deviation)
Unit of Measure: apparent diffusion coefficient
1.43  (0.07) 1.42  (0.09)
2.Secondary Outcome
Title Mortality Rates
Hide Description [Not Specified]
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 37 37
Measure Type: Number
Unit of Measure: participants
7 5
3.Secondary Outcome
Title Cerebellar Hemorrhage
Hide Description [Not Specified]
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 28 30
Measure Type: Number
Unit of Measure: participants
10 3
4.Secondary Outcome
Title Length of Time Requiring Invasive Respiratory Support
Hide Description [Not Specified]
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 37 37
Median (Inter-Quartile Range)
Unit of Measure: days
4
(1 to 22)
3
(1 to 22)
5.Secondary Outcome
Title Rates of Chronic Lung Disease
Hide Description Defined as oxygen requirement at 36 weeks PMA
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 37 37
Measure Type: Number
Unit of Measure: participants
19 18
6.Secondary Outcome
Title Rates of Necrotizing Enterocolitis
Hide Description [Not Specified]
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 37 37
Measure Type: Number
Unit of Measure: participants
6 5
7.Secondary Outcome
Title Rates of Retinopathy of Prematurity
Hide Description [Not Specified]
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 37 37
Measure Type: Number
Unit of Measure: participants
2 4
8.Secondary Outcome
Title Evaluation of EEG Seizure Burden
Hide Description For the first 72 hours of life, infants were monitored for seizures using continuous limited channel aEEG. Seizures were defined as a series of sharp waves, at least ten seconds in duration, which evolve in frequency, amplitude, and morphology over time and are clearly distinguishable from the background or artifact.
Time Frame First 72 hours of life
Hide Outcome Measure Data
Hide Analysis Population Description
7 patients excluded from high-dose group and 8 from standard-dose group due to recordings < 6 hours or corrupt data files.
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 30 29
Mean (Standard Deviation)
Unit of Measure: seconds
48.9  (97.1) 170.9  (413.1)
9.Secondary Outcome
Title Infant Neurobehavioral Scoring by Dubowitz Scale Prior to Discharge
Hide Description The Dubowitz Neurologic Examination is a standardized neurologic examination for infants at term age. It includes 6 compound optimality scores summed to obtain the total optimality score. Compound optimality scores include tone (range 0-10), tone pattern (range 0-5), reflexes (range 0-6), movements (range 0-3), abnormal signs (range 0-3), and behavior (range 0-7). The range for the compound optimality score is 0 - 34, with scores between 30.5 and 34 considered optimal and scores below 30.5 considered suboptimal.
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
9 patients excluded from high-dose group (7 died, 2 withdrew). 6 patients excluded from standard-dose group (5 died, 1 transferred).
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 28 31
Mean (Standard Deviation)
Unit of Measure: scores on a scale
17.4  (5.1) 18.7  (4.3)
10.Secondary Outcome
Title Bayley Scales of Infant Development Cognitive Score at 2 Years of Age
Hide Description The cognitive portion of the Bayley Scales of Infant Development assesses development in infants and toddlers between the ages of 0 and 3 years. Raw scores are converted to scale scores. A scale score of 100 is designed to represent the population mean. Scores below 100 represent developmental delay relative to the mean and scores above 100 represent advanced development relative to the mean.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
13 patients excluded from high-dose group (7 died, 2 withdrew, 2 we were unable to contact, 2 did not comply with scheduled appointments). 15 patients excluded from standard-dose group (5 died, 2 withdrew, 5 we were unable to contact, 3 did not comply with scheduled appointments).
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description:

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Overall Number of Participants Analyzed 24 22
Mean (Standard Deviation)
Unit of Measure: score
85.6  (11.6) 88.0  (8.4)
Time Frame Participants were followed for the duration of hospital stay, an average of 12 weeks.
Adverse Event Reporting Description Although we detected a higher incidence of cerebellar hemorrhage in the high dose caffeine group, we have not included this outcome measure as an adverse event as it was not identified a priori. This outcome is included in the results section.
 
Arm/Group Title High Dose Caffeine Standard Dose Caffeine
Hide Arm/Group Description

Loading dose 40mg/kg IV caffeine citrate, followed 12 hours later by 20mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate, followed 12 hours later by 10mg/kg IV caffeine citrate.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

Loading dose 20mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo, followed 12 hours later with 10mg/kg IV caffeine citrate, followed 12 hours later with D5W placebo.

Caffeine citrate: Caffeine to be administered as outlined to compare efficacy of different dosages.

All-Cause Mortality
High Dose Caffeine Standard Dose Caffeine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
High Dose Caffeine Standard Dose Caffeine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/37 (0.00%)   0/37 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
High Dose Caffeine Standard Dose Caffeine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/37 (0.00%)   0/37 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Terrie Inder
Organization: Brigham and Women's Hospital
Phone: 617-525-6650
EMail: tinder@partners.org
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00809055     History of Changes
Other Study ID Numbers: 08-0849
R01HD057098-01 ( U.S. NIH Grant/Contract )
HRPO 08-0849 ( Other Identifier: Washington University in St. Louis )
First Submitted: December 15, 2008
First Posted: December 16, 2008
Results First Submitted: December 17, 2015
Results First Posted: February 24, 2016
Last Update Posted: February 24, 2016