Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Women's Studies |
| Therapuetic Areas: | Neurology, Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 11/8/2017 |
| Start Date: | May 2009 |
| End Date: | November 2013 |
Phase II Study of Late- Versus Early Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants.
Intraventricular hemorrhage remains the most frequent, severe neurological complication of
prematurity, occurring in 25-30% of preterm infants. Post-hemorrhagic ventricular dilation
(PHVD) occurs in 25-50% of those infants, with over half requiring ventriculoperitoneal
shunts. When suboptimally untreated, PVHD results in a 3-4 fold increase in
neurodevelopmental delay. Despite the lifelong impact of PHVD on quality of life, little
research has been done over the past 20 years to improve patient outcomes.
The CENTRAL HYPOTHESIS of this project is that early treatment of PHVD will reduce
shunt-dependence and improve neurodevelopmental outcome in preterm infants.
prematurity, occurring in 25-30% of preterm infants. Post-hemorrhagic ventricular dilation
(PHVD) occurs in 25-50% of those infants, with over half requiring ventriculoperitoneal
shunts. When suboptimally untreated, PVHD results in a 3-4 fold increase in
neurodevelopmental delay. Despite the lifelong impact of PHVD on quality of life, little
research has been done over the past 20 years to improve patient outcomes.
The CENTRAL HYPOTHESIS of this project is that early treatment of PHVD will reduce
shunt-dependence and improve neurodevelopmental outcome in preterm infants.
Cranial ultrasound (CUS) is routinely performed on preterm infants ≤ 34 weeks estimated
gestational age (EGA) on day-of-life (DOL) #3 and again on DOL #7-10. Patients with Papile
Grade II-IV intraventricular hemorrhage (IVH) will undergo serial CUS 1-3 times weekly for 21
days following IVH to monitor for post-hemorrhagic ventricular dilation (PHVD). Using
standardized CUS parameters (Levene's ventricular index, Davies's diagonal anterior horn
width and thalamo-occipital diameter), infants will be offered enrollment in the trial when
their ventricular measures exceed the 97th percentile. Randomization to either low- or
standard-threshold PHVD treatment will be performed by opening sequentially numbered, sealed
envelopes. Envelopes will be prepared using a randomization schedule where allocations are
assigned in a 1:1 ratio in blocks of 4 so that the desired 1:1 ratio will be maintained at
periodic intervals in the study.
Neurosurgical treatment of progressive PHVD involves surgical placement of a ventricular
access device (VAD) for the removal of cerebrospinal fluid (CSF). Though at present clear
criteria do not exist for CSF removal, an estimation of usual neurosurgical practice and that
used in previous trials (standard-threshold) is intervention at Levene's EGA-adjusted 97th
percentile for ventricular enlargement + 4 mm or greater (> 2 standard deviations > 97th
percentile) or a diagonal width enlargement of the frontal horn > 10 mm. For the purpose of
this study, low-threshold intervention will be defined as ventricular enlargement > 97th
percentile with either a frontal diagonal width 7-10 mm or a thalamo-occipital diameter >24
mm.
CUS will be performed 2-3 times weekly in both the low- and standard-threshold groups. CSF
will be removed under sterile conditions via VAD taps (10 ml/kg over 20 minutes, 0-4 times
daily) as needed to maintain the CUS ventricular dimensions defined above for each treatment
group. Treatment group-specific ventricular size must be achieved within 48-72 hours of VAD
placement, and ventricles must be maintained within this range throughout the duration of
treatment.
If CSF removal is still required at 44 weeks EGA and there is consensus among the treating
neonatologist and neurosurgeon, permanent VP shunts will be surgically implanted. The rate of
VP shunts required by 44 weeks EGA and by 12 months corrected age will be monitored. Formal
neurodevelopmental evaluations will be performed by a blinded developmental psychologist at
18-24 months corrected age to assess neurocognitive and psychomotor function in low- versus
standard-threshold groups. Each infant will be scored using the Bayley Scales of Infant
Development.
gestational age (EGA) on day-of-life (DOL) #3 and again on DOL #7-10. Patients with Papile
Grade II-IV intraventricular hemorrhage (IVH) will undergo serial CUS 1-3 times weekly for 21
days following IVH to monitor for post-hemorrhagic ventricular dilation (PHVD). Using
standardized CUS parameters (Levene's ventricular index, Davies's diagonal anterior horn
width and thalamo-occipital diameter), infants will be offered enrollment in the trial when
their ventricular measures exceed the 97th percentile. Randomization to either low- or
standard-threshold PHVD treatment will be performed by opening sequentially numbered, sealed
envelopes. Envelopes will be prepared using a randomization schedule where allocations are
assigned in a 1:1 ratio in blocks of 4 so that the desired 1:1 ratio will be maintained at
periodic intervals in the study.
Neurosurgical treatment of progressive PHVD involves surgical placement of a ventricular
access device (VAD) for the removal of cerebrospinal fluid (CSF). Though at present clear
criteria do not exist for CSF removal, an estimation of usual neurosurgical practice and that
used in previous trials (standard-threshold) is intervention at Levene's EGA-adjusted 97th
percentile for ventricular enlargement + 4 mm or greater (> 2 standard deviations > 97th
percentile) or a diagonal width enlargement of the frontal horn > 10 mm. For the purpose of
this study, low-threshold intervention will be defined as ventricular enlargement > 97th
percentile with either a frontal diagonal width 7-10 mm or a thalamo-occipital diameter >24
mm.
CUS will be performed 2-3 times weekly in both the low- and standard-threshold groups. CSF
will be removed under sterile conditions via VAD taps (10 ml/kg over 20 minutes, 0-4 times
daily) as needed to maintain the CUS ventricular dimensions defined above for each treatment
group. Treatment group-specific ventricular size must be achieved within 48-72 hours of VAD
placement, and ventricles must be maintained within this range throughout the duration of
treatment.
If CSF removal is still required at 44 weeks EGA and there is consensus among the treating
neonatologist and neurosurgeon, permanent VP shunts will be surgically implanted. The rate of
VP shunts required by 44 weeks EGA and by 12 months corrected age will be monitored. Formal
neurodevelopmental evaluations will be performed by a blinded developmental psychologist at
18-24 months corrected age to assess neurocognitive and psychomotor function in low- versus
standard-threshold groups. Each infant will be scored using the Bayley Scales of Infant
Development.
Inclusion Criteria:
- Infants born at ≤ 34 weeks estimated gestational age with ultrasound-confirmed IVH
will be followed for eligibility.
- All infants with any grade IVH will be carefully followed with serial ultrasounds 1-3
times weekly to monitor ventricular measures.
- All infants with any grade IVH will be carefully followed for their ventricular
measures. If ventricular measures are crossing percentile lines toward the 90th then
the infant will be considered for recruitment as soon as the measures cross 97th.
Exclusion Criteria:
- Infants with congenital cerebral malformations
- Cystic periventricular leukomalacia
- CNS infection, metabolic disease
- PHVD present at birth will be excluded from the study.
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