? DESCRIPTION (provided by applicant): We estimate 250,000 new infants develop hydrocephalus, most commonly following neonatal infection, in sub- Saharan Africa (SSA) each year. Most have poor access to treatment. We have developed and validated a novel operative treatment for infant hydrocephalus combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) that avoids shunt dependence in the majority. Our prior collaborative work at CURE Children's Hospital of Uganda (CCHU) supports equipoise between shunt placement and ETV/CPC in regard to 5-year survival and neurocognitive development. That ETV/CPC prevents shunt dependence among those with no urgent access for shunt malfunction is compelling, but we do not know which treatment optimizes brain development. Going forward with humanitarian efforts to improve access to care for PIH infants in SSA, we seek to confirm the optimal treatment selection paradigm. Using data from CT imaging, we have found that both brain and CSF volume are significant multivariate discriminators of neurocognitive outcome. This method is promising as an objective measure of hydrocephalus treatment efficacy. Preliminary data from our R-21 funded (1R21TW009612) randomized controlled trial (RCT) of ETV/CPC vs. shunt for PIH treatment (ClinicalTrials.gov registration NCT01936272) have shown no important differences (either by intention-to-treat or actual treatment received) at this point in regard to safety, efficacy, or developmental outcome, thereby supporting completion of the study and extension of the follow up through the period of maximal brain growth at 24 months of age. This R01 proposes to accomplish the following aims: 1) further develop CCHU as an independent site for clinical hydrocephalus research; 2) test the hypothesis that treatment of PIH by ETV/CPC is better than or equal to shunting in regard to neurocognitive development; 3) correlate brain/CSF volume metrics with neurocognitive development; 4) assess the utility of preoperative brain/CSF volume metrics to guide treatment selection. The RCT initiated in the R- 21 study will be extended and completed. Of 100 required patients, 77 have been enrolled thus far with 6- month follow-up in 40 and none lost to follow-up. For all 100 patients, CT imaging preoperatively and at 6, 12, and 24 months postoperatively will be completed for brain and CSF volumetric assessment. Neurocognitive assessment with the Bayley Scales of Infant Development (BSID-III) will also be completed preoperatively, and at 6, 12, and 24 months post-operatively. Neurocognitive outcome will be correlated with pre- and post- operative brain/CSF volumes and treatment modality. Changes in brain and CSF volumes will also be correlated with treatment modality. Completion of the study will determine whether there is an important difference in developmental outcome between these two treatments. Significantly, demonstrating superiority of ETV/CPC or no important difference will lead to selecting ETV/CPC as the preferred initial treatment. Research capacity at CCHU will be further developed.
|Effective start/end date||7/22/15 → 5/31/20|
- National Institutes of Health: $591,345.00
- National Institutes of Health: $212,769.00
- National Institutes of Health: $283,752.00
- National Institutes of Health: $516,089.00
Africa South of the Sahara
Randomized Controlled Trials