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Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants (LETAP)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by Washington University School of Medicine.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00875758
First received: April 2, 2009
Last updated: August 3, 2011
Last verified: August 2011

April 2, 2009
August 3, 2011
May 2009
May 2013   (final data collection date for primary outcome measure)
Ventriculoperitoneal shunt-dependence [ Time Frame: One year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00875758 on ClinicalTrials.gov Archive Site
  • Shunt malfunction [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Unnecessary device implantation [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Shunt infection [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Neurodevelopmental Outcome [ Time Frame: 18-24 months of age ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prematurity
  • Intraventricular Hemorrhage
  • Hydrocephalus
  • 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.
  • Active Comparator: Standard threshold
    Intervention: Procedure: Removal of CSF through ventricular access device
  • Experimental: Low-threshold
    Intervention: Procedure: Removal of CSF through a ventricular access device

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
May 2014
May 2013   (final data collection date for primary outcome measure)

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.
Both
up to 34 Weeks
No
Contact: David D Limbrick, MD, PHD 314-454-2810 limbrickd@nsurg.wustl.edu
Contact: Deanna Mercer, CCRC 314-454-5498 mercerd@wudosis.wustl.edu
United States
 
NCT00875758
LETAP-09-0380
Yes
David Limbrick, M.D., Ph.D., Washington University in St. Louis
Washington University School of Medicine
Not Provided
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
Washington University School of Medicine
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP