Effects of Caffeine on Intermittent Hypoxia in Infants Born Preterm

• ClinicalTrials.gov Identifier: NCT01875159
• Recruitment Status: Completed
• First Posted: June 11, 2013
• Results First Posted: March 17, 2015
• Last Update Posted: March 17, 2015
• Sponsor: American SIDS Institute
• Information provided by (Responsible Party): Carl Hunt, American SIDS Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypoxia
• Intervention: Drug: Caffeine citrate 6 mg/kg/day
• Enrollment: 98

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Caffeine	Active Comparator: no Caffeine
Arm/Group Description	Caffeine citrate 6 mg/kg/day Caffeine citrate 6 mg/kg/day: Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age.	Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care) in regard to extent of intermittent hypoxia from 35 weeks postmenstrual age (PMA) to 40 weeks PMA.
Period Title: Overall Study
Started	45	53
Completed	42	53
Not Completed	3	0

Baseline Characteristics

Arm/Group Title		Caffeine	Active Comparator: no Caffeine	Total
Arm/Group Description		Caffeine citrate 6 mg/kg/day Caffeine citrate 6 mg/kg/day: Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age.	Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care) in regard to extent of intermittent hypoxia from 35 weeks postmenstrual age (PMA) to 40 weeks PMA.	Total of all reporting groups
Overall Number of Baseline Participants		45	53	98
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Mean (Standard Deviation); Unit of measure: Weeks
Gestational Age	Number Analyzed	45 participants	53 participants	98 participants
		28.6 (1.7)	29.1 (1.7)	28.9 (1.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	53 participants	98 participants
	Female	21 46.7%	26 49.1%	47 48.0%
	Male	24 53.3%	27 50.9%	51 52.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	53 participants	98 participants
	Hispanic or Latino	2 4.4%	8 15.1%	10 10.2%
	Not Hispanic or Latino	40 88.9%	45 84.9%	85 86.7%
	Unknown or Not Reported	3 6.7%	0 0.0%	3 3.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	53 participants	98 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	2 4.4%	0 0.0%	2 2.0%
	Black or African American	11 24.4%	9 17.0%	20 20.4%
	White	27 60.0%	42 79.2%	69 70.4%
	More than one race	2 4.4%	0 0.0%	2 2.0%
	Unknown or Not Reported	3 6.7%	2 3.8%	5 5.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	45 participants	53 participants	98 participants
		45	53	98
Mean birth weight; Mean (Standard Deviation); Unit of measure: Grams
	Number Analyzed	45 participants	53 participants	98 participants
		1262.1 (265.6)	1274.5 (270.3)	1270.1 (267.2)

Outcome Measures

1. Primary Outcome

Title	Episodes of Intermittent Hypoxia Per Hour
Description	Number of episodes of Intermittent hypoxia per hour of pulse oximeter recording less than 90% oxygen saturation
Time Frame	35, 36, 37, 38 weeks postmenstrual age

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Caffeine	Active Comparator: no Caffeine
Arm/Group Description:	Caffeine citrate 6 mg/kg/day Caffeine citrate 6 mg/kg/day: Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age.	Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care) in regard to extent of intermittent hypoxia from 35 weeks postmenstrual age (PMA) to 40 weeks PMA.
Overall Number of Participants Analyzed	42	53
Mean (Standard Deviation); Unit of Measure: Events per hour
Week 35	3.6 (4.3)	8.4 (8.4)
Week 36	3.8 (4.5)	8.2 (11.5)
Week 37	4.3 (5.9)	5.2 (6.8)
Week 38	4.2 (5.7)	4.7 (6.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caffeine, Active Comparator: no Caffeine
	Comments	>80% probability of detecting at least a 36% reduction in intermittent hypoxia events/hour of recording and in sec/hour <90% oxygen saturation/hour of recording
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	GEE gamma regression models
	Comments	[Not Specified]

2. Primary Outcome

Title	Number of Seconds of Intermittent Hypoxia Per Hour
Description	Number of seconds of Intermittent hypoxia per hour of pulse oximeter recording less than 90% oxygen saturation
Time Frame	35, 36, 37, 38 weeks postmenstrual age

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Caffeine	Active Comparator: no Caffeine
Arm/Group Description:	Caffeine citrate 6 mg/kg/day Caffeine citrate 6 mg/kg/day: Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age.	Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care) in regard to extent of intermittent hypoxia from 35 weeks postmenstrual age (PMA) to 40 weeks PMA.
Overall Number of Participants Analyzed	42	53
Mean (Standard Deviation); Unit of Measure: seconds per hour
Week 35	50.9 (48.1)	106.3 (89.0)
Week 36	49.5 (52.1)	100.1 (114.6)
Week 37	58.8 (74.1)	66.8 (75.2)
Week 38	69.3 (108.8)	66.0 (74.8)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Caffeine		Active Comparator: no Caffeine
Arm/Group Description	Caffeine citrate 6 mg/kg/day Caffeine citrate 6 mg/kg/day: Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age.		Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care) in regard to extent of intermittent hypoxia from 35 weeks postmenstrual age (PMA) to 40 weeks PMA.
All-Cause Mortality
	Caffeine		Active Comparator: no Caffeine
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Caffeine		Active Comparator: no Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0.00%)		0/53 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Caffeine		Active Comparator: no Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/42 (11.90%)		0/53 (0.00%)
Cardiac disorders
Tachycardia †	5/42 (11.90%)	5	0/53 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Carl E. Hunt, M.D.
• Organization: Uniformed Services University
• Phone: 240-694-2676
• EMail: carl.hunt@usuhs.edu

Publications of Results:

Rhein LM, Dobson NR, Darnall RA, Corwin MJ, Heeren TC, Poets CF, McEntire BL, Hunt CE; Caffeine Pilot Study Group. Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial. JAMA Pediatr. 2014 Mar;168(3):250-7. doi: 10.1001/jamapediatrics.2013.4371.

• Responsible Party: Carl Hunt, American SIDS Institute
• ClinicalTrials.gov Identifier: NCT01875159 History of Changes
• Other Study ID Numbers: ASI 01
• First Submitted: June 3, 2013
• First Posted: June 11, 2013
• Results First Submitted: January 14, 2014
• Results First Posted: March 17, 2015
• Last Update Posted: March 17, 2015