Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants

NCT ID: NCT00875758

Last Updated: 2017-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2013-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Intraventricular Hemorrhage Hydrocephalus

Keywords

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preterm infants IVH germinal matrix intraventricular hemorrhage hydrocephalus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard threshold

Group Type ACTIVE_COMPARATOR

Removal of CSF through ventricular access device

Intervention Type PROCEDURE

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.

Low-threshold

Group Type EXPERIMENTAL

Removal of CSF through a ventricular access device

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Maximum Eligible Age

34 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David D Limbrick, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Amit Mathur, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Terrie Inder, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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de Vries LS, Liem KD, van Dijk K, Smit BJ, Sie L, Rademaker KJ, Gavilanes AW; Dutch Working Group of Neonatal Neurology. Early versus late treatment of posthaemorrhagic ventricular dilatation: results of a retrospective study from five neonatal intensive care units in The Netherlands. Acta Paediatr. 2002;91(2):212-7. doi: 10.1080/080352502317285234.

Reference Type BACKGROUND
PMID: 11952011 (View on PubMed)

Brouwer A, Groenendaal F, van Haastert IL, Rademaker K, Hanlo P, de Vries L. Neurodevelopmental outcome of preterm infants with severe intraventricular hemorrhage and therapy for post-hemorrhagic ventricular dilatation. J Pediatr. 2008 May;152(5):648-54. doi: 10.1016/j.jpeds.2007.10.005. Epub 2007 Dec 26.

Reference Type BACKGROUND
PMID: 18410767 (View on PubMed)

Other Identifiers

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LETAP-09-0380

Identifier Type: -

Identifier Source: org_study_id