Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants (LETAP)
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.
|Intraventricular Hemorrhage Hydrocephalus||Procedure: Removal of CSF through ventricular access device Procedure: Removal of CSF through a ventricular access device||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Late- Versus Early Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants.|
- Ventriculoperitoneal shunt-dependence [ Time Frame: One year ]
- Shunt malfunction [ Time Frame: 4 years ]
- Unnecessary device implantation [ Time Frame: One year ]
- Shunt infection [ Time Frame: One year ]
- Neurodevelopmental Outcome [ Time Frame: 18-24 months of age ]
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
|Active Comparator: Standard threshold||
Procedure: Removal of CSF through ventricular access device
Ventricular access devices (VADs) are surgically implanted when cranial ultrasound measures reach treatment group-specific criteria. For the standard-threshold arm, VADs will be implanted when the age-adjusted ventricular index shows the ventricles to be at the 97th percentile + 2 standard deviations. Cerebrospinal fluid is then removed from the VADs 1-3 times daily as required to maintain ventricles within these parameters.
Procedure: Removal of CSF through a ventricular access device
Ventricular access devices (VADs) are surgically implanted when cranial ultrasound measures reach treatment group-specific criteria. For the standard-threshold arm, VADs will be implanted when the age-adjusted ventricular index shows the ventricles to be at the 97th percentile. Cerebrospinal fluid is then removed from the VADs 1-3 times daily as required to maintain ventricles within these parameters.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00875758
|United States, Missouri|
|St. Louis Children's Hospital|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||David D Limbrick, MD, PhD||Washington University School of Medicine|
|Principal Investigator:||Amit Mathur, MD||Washington University School of Medicine|
|Principal Investigator:||Terrie Inder, MD||Washington University School of Medicine|