Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202209722364968 Date of Approval: 21/09/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Prospective study evaluating the efficacy of ventricular irrigation in the treatment of the bacterial ventriculitis (VIP STUDY)
Official scientific title Prospective study evaluating the efficacy of ventricular irrigation in the treatment of the bacterial ventriculitis (VIP STUDY)
Brief summary describing the background and objectives of the trial Introduction and Background Bacterial ventriculitis typically occurs in the neonatal and early infancy when bacteria gain access to the brain ventricles. This is closely linked to neonatal sepsis and likewise to factors associated with poor perinatal outcomes prevalent in Low- Middle Income Countries (LMICs). Bacterial ventriculitis can result into brain damage, complex hydrocephalus and neuro-disability. Currently antibiotic therapy is the mainstay of treatment, however because of an immature neonatal immunity, poor CSF penetration and increasing antibiotic resistance the time to achieving sterile CSF is often prolonged and delays definitive therapy for hydrocephalus. Ventricular irrigation has been shown to improve cure rates in multidrug resistant GN ventriculitis by reducing the bacterial load, dampening the immunological response which may translate into less brain damage and minimal intraventricular septa formation. We intend to study the efficacy of ventricular irrigation among infants undergoing treatment for ventriculitis at CURE Children’s Hospital of Uganda. Primary Objective To determine whether ventricular irrigation in addition to parenteral antibiotics improves time to CSF sterilization, time to definitive surgery and 30-day mortality rates of infants treated for bacterial ventriculitis at CCHU compared to the standard of care (parenteral antibiotics) Specific Objectives 1. To Determine the time to CSF Sterilization following ventricular irrigation compared to standard antibiotic treatment. 2. To compare 30-day mortality rates between the study arms, ventricular irrigation versus standard antibiotic treatment. 3. To determine the time to definitive surgical intervention following ventricular Irrigation versus standard antibiotic treatment. 4. To determine the neurological outcomes following ventricular irrigation
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VIP
Disease(s) or condition(s) being studied Infections and Infestations,Nervous System Diseases,Paediatrics,Surgery
Sub-Disease(s) or condition(s) being studied Bacterial Ventriculitis
Purpose of the trial Treatment: Surgery
Anticipated trial start date 03/10/2022
Actual trial start date
Anticipated date of last follow up 03/11/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 240
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Parenteral Antibiotics standard of care Empirical antibiotics per kilogram body weight will be administered at the time of diagnosis. Control group will be randomized to only parenteral antibiotics (PAT) which is the standard of care for bacterial ventriculitis that they will recieve for two weeks or more. Empirical antibiotics will be administered at the time of diagnosis. The choice of empirical antibiotics will be guided by the current CCHU antibiotics management protocols. Empirical antibiotics administration will not be for a duration longer than 72 hours. Subsequent definitive parenteral antibiotics treatment will be based on the bacteriological culture profile. Parenteral antibiotics will be used for not less than two weeks. 120 Active-Treatment of Control Group
Experimental Group Ventricular Irrigation and Parenteral Antibiotics VT group Surgical Intervention of Ventricular Irrigation and Aspiration Surgical Intervention of Ventricular Irrigation and Aspiration. Ventricular Irrigation and Parenteral Antibiotics (VT) In addition to Parenteral Antiobiotics the participants will also have Ventricular Irrigation done. The following composition of warm (room temperature?) Ringer’s lactate solution with antibiotic (500mls Ringer’s lactate with 160mg Gentamycin) will be used for lavage/ irrigation. For the endoscopic irrigation/ lavage Karl Storz fiberscope, MVM, series 11xx BN1, Tuttlingen, Germany will be used. As part of standard protocol, all patients due to undergo Ventricular irrigation are given a loading dose of anticonvulsants; using Intravenous phenobarbitone, at induction of Anaesthesia. Under general Anaesthesia patient is positioned supine with head neutral or left lateral. The surgical site is prepped and draped. The skin incision is positioned over the intersection of mid-pupillary line and tragus on the right side or both left and right side if right and left lateral ventricles were not communicating. A durotomy and corticectomy are done. Using either brain needles or a flexible neuro endoscope the lateral ventricles are accessed. Cerebrospinal fluid is taken for analysis. The macroscopic appearance of cerebrospinal fluid is observed. Using 20cc syringes, Ringer’s lactate is flushed into ventricular system and aspirated via the brain needle or endoscope. Irrigation will stop when macroscopic appearance of ventricular fluid was near clear. The skin is closed in layers. All biological samples will be obtained and analyzed according to the CCHU hospital and laboratory SOP’s. 120
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
All patients zero to twelve month of age admitted with a diagnosis of bacterial ventriculitis will be included 1. Age 0 days to 12 months 2. Any patient with clinical and laboratory evidence of bacterial ventriculitis 1. Any eligible patient whose caregiver declines participation in the study. 2. Any patient that does not meet the inclusion criteria listed above. 3. Any patient with ventriculitis not attributed to a bacterial cause. 4. Any eligible patient from distant locations especially out of Uganda. Infant: 0 Month(s)-12 Month(s),New born: 0 Day-1 Month 0 Day(s) 12 Month(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 21/09/2022 CURE Childrens Hospital of Uganda Research Ethics Commitee
Ethics Committee Address
Street address City Postal code Country
Plot 97-105 Mbale 00000 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to sterilization of CSF. This will be determined as the time in days taken from intervention to sterilization of CSF First CSF analysis results indicating normal parameters. After diagnosis and Intervention CSF analysis will be done every 3 days upto normal CSF parameters.
Secondary Outcome Time in days to definitive Surgical Intervention Time in days to when a definitive surgical intervention like a CSF diversion is done.
Secondary Outcome All cause mortality rates between study arms at 30 days post intervention All cause mortality rates between study arms measured at 30 days post diagnosis and intervention.
Secondary Outcome Neurological outcome between the study arms; new onset seizures, delayed or regression of developmental milestones, new onset neurological deficits measured through out the study period.
Secondary Outcome Radiological evidence of disease progression after intervention Measured through the study period
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CURE Childrens Hospital of Uganda Plot 97-105 Mbale 00000 Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Cure Childrens Hospital of Uganda Plot 97-105 Mbale 00000 Uganda
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Cure Childrens Hospital of Uganda Plot 97-105 Mbale 00000 Uganda Hospital
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Humphrey Okechi humphreyokechi@gmail.com +256779372445 Plot 97-105
City Postal code Country Position/Affiliation
Mbale 00000 Uganda Neuro Surgeon
Role Name Email Phone Street address
Public Enquiries Betty Nantongo nantongo109@gmail.com +256776415246 Plot 97-105, Bugwere Road
City Postal code Country Position/Affiliation
Mbale 00000 Uganda Anaesthesiologist
Role Name Email Phone Street address
Scientific Enquiries Emmanuel Wegoye wegoye1981@gmail.com +256772587359 Plot 97-105, Bugwere Road
City Postal code Country Position/Affiliation
Mbale 00000 Uganda Neuro Surgeon
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data obtained from the study maybe provide to qualified researchers interested in Paediatric Neuro Surgery. Only data that is De identified will be shared after approval of request and execution of a Data Sharing Agreement with the requesting party. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Data requests ca be submitted immediately after article publication and will be accessible up to 5 years following article publication Access to trial Individual Data will be requested by qualified researchers and will be provided only after review and approval of a research proposal and statistical analysis plan and execution of a Data Sharing Agreement.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information