- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00875758
Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants (LETAP)
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.
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- St. Louis Children's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Standard threshold
|
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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Ventriculoperitoneal shunt-dependence
Time Frame: One year
|
One year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Shunt malfunction
Time Frame: 4 years
|
4 years
|
Unnecessary device implantation
Time Frame: One year
|
One year
|
Shunt infection
Time Frame: One year
|
One year
|
Neurodevelopmental Outcome
Time Frame: 18-24 months of age
|
18-24 months of age
|
Collaborators and Investigators
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
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LETAP-09-0380
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Intraventricular Hemorrhage
-
Sharp HealthCareEunice Kennedy Shriver National Institute of Child Health and Human Development...Completed
-
Children's Hospital Medical Center, CincinnatiRecruitingIntraventricular HemorrhageUnited States
-
Nanjing PLA General HospitalUnknownIntraventricular Hemorrhage, Endoscopic Intraventricular Evacuation Surgery, Extraventricular DrainageChina
-
University of Rhode IslandNational Institute of Nursing Research (NINR); Brown University; Women and Infants...CompletedSepsis | Intraventricular HemorrhageUnited States
-
Icahn School of Medicine at Mount SinaiIRRASRecruiting
-
Mount Sinai Hospital, CanadaLondon Health Sciences Centre; Royal Alexandra Hospital; Foothills Medical CentreNot yet recruitingIntraventricular Hemorrhage of Newborn Grade 2 | Intraventricular Hemorrhage of Newborn Grade 3 | Intraventricular Haemorrhage Grade IVCanada
-
Johns Hopkins UniversityEunice Kennedy Shriver National Institute of Child Health and Human Development...RecruitingIntraventricular Hemorrhage of PrematurityUnited States
-
Albert Einstein College of MedicineUniversity of Pittsburgh; Brigham and Women's Hospital; Wake Forest University... and other collaboratorsWithdrawnIntraventricular Hemorrhage of PrematurityUnited States
-
Sharp HealthCareEunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedIntraventricular HemorrhageUnited States
-
National Taiwan University HospitalCompletedNursing Caries | Intraventricular Hemorrhage of PrematurityTaiwan
Clinical Trials on Removal of CSF through ventricular access device
-
General Hospital GroeningeCompletedOncology | Haematological MalignancyBelgium
-
Université de SherbrookeCompletedDifficult IntubationCanada
-
Paracor Medical, IncTerminatedHeart Failure, CongestiveUnited States
-
Medical College of WisconsinCompletedEndothelial Dysfunction | Heart Failure With Reduced Ejection Fraction | LVADUnited States
-
University of Kansas Medical CenterNational Institute for Biomedical Imaging and Bioengineering (NIBIB)CompletedMalnutrition | Malabsorption | Short Bowel SyndromeUnited States
-
Universitätsklinikum Hamburg-EppendorfOvesco Endoscopy AGSuspendedSubmucosal Tumor of StomachGermany
-
Boston Scientific CorporationCompletedHeart FailureUnited States
-
University of ThessalyAttikon HospitalCompleted
-
University Hospital, BrestCompletedHypoxemic Acute Respiratory Distress | Infant Between 1 Month and 24 Months Old | Child Between 2 and 15 Years OldFrance
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Celgene; Aduro Biotech, Inc.Active, not recruitingMultiple MyelomaUnited States