Jaundice, Neonatal
Conditions
Keywords
Hyperbilirubinemia, Neonatal
Brief summary
At present, much of sub-Saharan Africa, including Nigeria and other resource-limited countries, are without ready access to CPT, due to factors including the lack of PT devices, which are expensive and require consistent electric power to operate. NHB is a significant cause of neonatal morbidity and mortality, but preventable when appropriate treatment is initiated. We have shown that FS-PT is safe and efficacious for the treatment of mild-moderate NHB. The major goal of this study is to demonstrate that FS-PT is efficacious for the treatment of significant/severe NHB, generally defined as TB of ≥12-14mg/dL (but more specially as defined as needing phototherapy per American Academy of Pediatric 2004 guidelines). This arm was done at 1 site in Nigeria (in Ogbomoso). The rationale for conducting the study is that in Nigeria, and other countries that cannot afford effective commercial light devices and/or have no reliable electric power to operate them, filtered sunlight phototherapy might offer a safe and effective treatment for neonatal jaundice.
Detailed description
Severe neonatal hyperbilirubinemia (NHB) and its progression to kernicterus is a leading cause of deaths and disabilities among newborns in the developing world, particularly in sub-Saharan Africa including Nigeria. Many infants live in villages/towns far from clinical facilities capable of providing conventional artificial blue light phototherapy (CPT) which is the standard treatment for NHB in the industrialized world. Hence, more babies succumb to this preventable tragedy principally on account of lack of electricity and/or available/affordable CPT. To make treatment of NHB more readily available, we designed and tested a novel, yet simple, practical alternative device to deliver blue light PT in underserved areas from filtered sunlight. The investigators pilot study demonstrated that appropriately filtered sunlight phototherapy (FS-PT) not only offers safe and affordable treatment for infants with mild-moderate NHB, but is also no less efficacious than CPT. Other studies have shown faster decline at higher bilirubin (TB) levels and with higher irradiances. The next logical step to move this urgently needed and exciting therapy forward is to test FS-PT in infants with significant/severe NHB as defined by the American Academy of Pediatrics (AAP) criteria for high-risk infants. In doing so, the investigators will potentially be preventing acute bilirubin encephalopathy (ABE) and kernicterus in many of these infants.
Interventions
Infants will receive \>= four hours per day of filtered-sunlight phototherapy for 1 to 10 days. The filtering will be done using Air Blue 80 window tinting film.
DEVICEIntensive phototherapy
Infants will receive \>= four hours per day of intensive phototherapy for 1 to 10 days.
Sponsors
Thrasher Research Fund
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Intervention model description
Non-inferiority trial comparing the two methods of phototherapy
Eligibility
Sex/Gender
ALL
Age
No minimum to 14 Days
Healthy volunteers
Yes
Inclusion criteria
* Subjects will be eligible to participate in the study if all of the following conditions exist: 1. At time of birth, infant is \> 35 weeks gestation (or ≥ 2.2 kg if gestational age is not available. 2. Infant is \< 14 days old at the time of enrollment. 3. Infant has an elevated TB defined as at the level recommended for high-risk infants per AAP guidelines or higher. 4. Parent or guardian has given consent for the infant to participate.
Exclusion criteria
* Subjects will be excluded from enrollment in the study if any of the following conditions exist: 1. Infants with a condition requiring referral for treatment not available at the hospital study site. 2. Infants with a life-expectancy of \< 24 hours at screening enrollment. 3. Infants requiring oxygen therapy unless that can be provided while under PT. 4. Infants clinically dehydrated or sunburned at the time of screening enrollment. 5. Infants with a temperature \< 36.0 or \> 37.5 degrees Centigrade that does not return to normothermia within 1 hour.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Phototherapy | 2 to 10 days | For a given evaluable treatment day, the phototherapy treatment was deemed effective if that infant on that day had a decrease in serum bilirubin level or (if \<72hrs old) an rate of increase of less than 0.2 mg/dL/h. Therefore efficacy is reported as a percentage of the evaluable treatment days (i.e. number of effective evaluable treatment days divided by total number of evaluable treatment days). |
| Safety of Phototherapy | 2 to 10 days | For a given treatment day, the phototherapy treatment was deemed safe if that infant on that day did not have to be withdrawn from treatment due to hypo- or hyperthermia, sunburn or dehydration. Therefore safety is reported as a percentage of the total treatment days (i.e. number of safe treatment days divided by total number of treatment days). |
Countries
Nigeria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Filtered-sunlight Phototherapy Infants will receive \>= four hours per day of filtered-sunlight phototherapy for 1 to 10 days. The filtering will be done using Air Blue 80 window tinting film.
Filtered-sunlight phototherapy: Infants will receive \>= four hours per day of filtered-sunlight phototherapy for 1 to 10 days. The filtering will be done using Air Blue 80 window tinting film. | 87 |
| Intensive Phototherapy Infants will receive \>= four hours per day of intensive phototherapy for 1 to 10 days.
Intensive phototherapy: Infants will receive \>= four hours per day of intensive phototherapy for 1 to 10 days. | 87 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Direct hyperbilirubinemia | 0 | 2 |
| Overall Study | Needed treatment incompatible with PT | 1 | 1 |
| Overall Study | Parent request | 4 | 1 |
Baseline characteristics
| Characteristic | Filtered-sunlight Phototherapy | Intensive Phototherapy | Total |
|---|---|---|---|
| Age, Continuous | 47 hours | 59 hours | 57 hours |
| Sex: Female, Male Female | 34 Participants | 30 Participants | 64 Participants |
| Sex: Female, Male Male | 52 Participants | 56 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 87 | 0 / 87 |
| serious Total, serious adverse events | 0 / 87 | 0 / 87 |
Outcome results
Primary
Efficacy of Phototherapy
For a given evaluable treatment day, the phototherapy treatment was deemed effective if that infant on that day had a decrease in serum bilirubin level or (if \<72hrs old) an rate of increase of less than 0.2 mg/dL/h. Therefore efficacy is reported as a percentage of the evaluable treatment days (i.e. number of effective evaluable treatment days divided by total number of evaluable treatment days).
Time frame: 2 to 10 days
Population: The efficacy analysis used all treatment days where an infant received \>=4h of PT and both bilirubin levels were available. 87 infants received 215 treatment days of FSPT, but only 133 of those days (in 79 infants) were analyzable for efficacy. Similarly, 87 infants received 219 days of IntPT, but only 152 days (in 83 infants) were analyzable.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Filtered-sunlight Phototherapy | Efficacy of Phototherapy | 116 treatment days |
| Intensive Phototherapy | Efficacy of Phototherapy | 135 treatment days |
Primary
Safety of Phototherapy
For a given treatment day, the phototherapy treatment was deemed safe if that infant on that day did not have to be withdrawn from treatment due to hypo- or hyperthermia, sunburn or dehydration. Therefore safety is reported as a percentage of the total treatment days (i.e. number of safe treatment days divided by total number of treatment days).
Time frame: 2 to 10 days
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Filtered-sunlight Phototherapy | Safety of Phototherapy | 215 treatment days |
| Intensive Phototherapy | Safety of Phototherapy | 219 treatment days |