Intraventricular HemorrhageLETAPNCT00875758
Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants
A study testing Removal of CSF through ventricular access device and Removal of CSF through a ventricular access device in people with Intraventricular Hemorrhage and Hydrocephalus, run by Washington University School of Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 34 weeks
- Conditions the study is for
- Intraventricular Hemorrhage, Hydrocephalus
- What is being tested?
- Removal of CSF through ventricular access device and Removal of CSF through a ventricular access device
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Nov 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 34 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- Infants with congenital cerebral malformations
- Cystic periventricular leukomalacia
- CNS infection, metabolic disease
- PHVD present at birth will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Louis Children's Hospital
St Louis, Missouri, 63110
About this study
Official title: 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.
Read the 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.
- Conditions
- Intraventricular Hemorrhage, Hydrocephalus
- Being tested
- Removal of CSF through ventricular access device, Removal of CSF through a ventricular access device
- Keywords
- preterm infants, IVH, germinal matrix, intraventricular hemorrhage, hydrocephalus
- Medical subject headings
- Hydrocephalus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Removal of CSF through ventricular access deviceProcedure or surgery
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.
Removal of CSF through a ventricular access deviceProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard threshold | Active comparator | Not described Receives: Procedure: Removal of CSF through ventricular access device |
| Low-threshold | Experimental | Not described Receives: Procedure: Removal of CSF through a ventricular access device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventriculoperitoneal shunt-dependence
Measured: One year
Secondary outcomes (4)
Shunt malfunction
Measured: 4 years
Unnecessary device implantation
Measured: One year
Shunt infection
Measured: One year
Neurodevelopmental Outcome
Measured: 18-24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intraventricular HemorrhageStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David D Limbrick, MD, PhD, Principal investigator, Washington University School of MedicineAmit Mathur, MD, Principal investigator, Washington University School of MedicineTerrie Inder, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00875758
- Sponsor's protocol ID
- LETAP-09-0380
- Acronym
- LETAP
- Status last verified
- Nov 2017
- First submitted
- 2 Apr 2009
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 11952011Brouwer 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.
PubMed 18410767
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Late- Versus Early Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants.
- ClinicalTrials.gov ID
- NCT00875758
- Acronym / sponsor ID
- LETAP / LETAP-09-0380
- Conditions
- Intraventricular Hemorrhage, Hydrocephalus
- Keywords
- preterm infants, IVH, germinal matrix, intraventricular hemorrhage, hydrocephalus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 3 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard threshold | Active comparator | Procedure: Removal of CSF through ventricular access device |
| Low-threshold | Experimental | Procedure: Removal of CSF through a ventricular access device |
Who may qualify
- Ages
- Up to 34 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- Infants with congenital cerebral malformations
- Cystic periventricular leukomalacia
- CNS infection, metabolic disease
- PHVD present at birth will be excluded from the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Removal of CSF through ventricular access deviceVentricular 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 or surgery | Standard threshold |
| Removal of CSF through a ventricular access deviceVentricular 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. | Procedure or surgery | Low-threshold |
Primary outcome
Ventriculoperitoneal shunt-dependence
Time frame: One year
4 secondary outcomes
Shunt malfunction
Time frame: 4 years
Unnecessary device implantation
Time frame: One year
Shunt infection
Time frame: One year
Neurodevelopmental Outcome
Time frame: 18-24 months of age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Background: PubMed 11952011de 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.
- Background: PubMed 18410767Brouwer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David D Limbrick, MD, PhD principal investigator
Washington University School of Medicine
Amit Mathur, MD principal investigator
Washington University School of Medicine
Terrie Inder, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Removal of CSF through ventricular access device and Removal of CSF through a ventricular access device in people with Intraventricular Hemorrhage and Hydrocephalus, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventriculoperitoneal shunt-dependence (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00875758, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.