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
  Purpose

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.


Condition Intervention Phase
Prematurity
Intraventricular Hemorrhage
Hydrocephalus
Procedure: Removal of CSF through ventricular access device
Procedure: Removal of CSF through a ventricular access device
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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.

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Ventriculoperitoneal shunt-dependence [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 50
Study Start Date: May 2009
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Experimental: Low-threshold 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 34 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00875758

Contacts
Contact: David D Limbrick, MD, PHD 314-454-2810 limbrickd@nsurg.wustl.edu
Contact: Deanna Mercer, CCRC 314-454-5498 mercerd@wudosis.wustl.edu

Locations
United States, Missouri
St. Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: David D Limbrick, MD, PhD    314-454-2810    limbrickd@nsurg.wustl.edu   
Contact: Deanna Mercer, CCRC    314-454-5498    mercerd@wudosis.wustl.edu   
Principal Investigator: David D Limbrick, MD, PhD         
Principal Investigator: Amit Mathur, MD         
Principal Investigator: Terrie Inder, MD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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
  More Information

Publications:
Responsible Party: David Limbrick, M.D., Ph.D., Washington University in St. Louis
ClinicalTrials.gov Identifier: NCT00875758     History of Changes
Other Study ID Numbers: LETAP-09-0380
Study First Received: April 2, 2009
Last Updated: August 3, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
preterm infants
IVH
germinal matrix
intraventricular hemorrhage
hydrocephalus

Additional relevant MeSH terms:
Hemorrhage
Hydrocephalus
Cerebral Hemorrhage
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Intracranial Hypertension
Intracranial Hemorrhages
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2014