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.: PACTR202112749708968 Date of Approval: 20/12/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Evaluating the combined use of non-invasive respiratory support alongside preventative anticonvulsant treatment in children presenting to hospital with cerebral malaria and convulsions
Official scientific title Evaluating the combined use of NOn-invasive Ventilation alongside preventative anticonvulsant treatment In children presenting to hospital with CErebral_Malaria and convulsions: a phase I trial
Brief summary describing the background and objectives of the trial One of the most severe complications of severe malaria in children is cerebral malaria, which occurs when a person with malaria becomes unconscious because of the infection. Children who develop cerebral malaria have a high risk of death, and those that survive have a risk of long-term neurological disability. Children with cerebral malaria who have repeated seizures have an even higher risk of poor outcomes. Because of this, research studies have been conducted to determine if the preventative (prophylactic) use of medications to control seizure activity (anticonvulsants), can improve outcomes in children with cerebral malaria. However, the lead to children developing breathing problems. An important question is whether the provision of breathing (ventilatory) support in addition to prophylactic anticonvulsants is effective in terms of preventing respiratory arrest and reducing neurological injury associated with seizures, and whether this strategy can reduce mortality and long-term disability in children with cerebral malaria. Biphasic cuirass ventilation (BCV) is a mode of ventilatory support that provides both negative and positive pressure to the chest wall, supports both the inspiratory and expiratory phases of breathing. The aim of this project is to develop a protocol for the use of BCV in combination with prophylactic levetiracetam, within a Phase I trial in children with cerebral malaria admitted to the high dependency ward in Kilifi, Kenya. The Phase I trial will generate feasibility, safety and preliminary efficacy data, which will inform the design of a larger Phase II study to test this intervention.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) NOVICE M Trial
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Supportive care
Anticipated trial start date 01/01/2019
Actual trial start date 03/02/2020
Anticipated date of last follow up 31/08/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants)
Recruitment status 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
Crossover: all participants receive all interventions in different sequence during study Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group BiCurass Ventilation as required until child no longer in coma Biphasic cuirass ventilation (BCV) is a mode of ventilatory support that provides both negative and positive pressure to the chest wall. This non-invasive system thereby supports both the inspiratory (the negative pressure expands the chest for the in-breath) and expiratory phases (the positive pressure assists with the outbreath) of breathing. The system is portable, does not require insertion of an invasive airway tube ( intubation), and can be used across a wide weight and age range. BCV has been used to support ventilation in children with profound neuromuscular weakness and chest wall disorders at home. If proven to be safe, feasible and effective in children with cerebral malaria, this system of ventilator support could be widely implemented in resource-limited settings. 10 Active-Treatment of Control Group
Experimental Group Leveteracitam low dose Intravenous 40 mg/kg loading dose and the 30mg/kg every 12 hours For 3 days or until coma resolution (when the child is able to sit unsupported or breast feed if under 6 months). Prophylactic anticonvulsant treatment to prevent seizures to be given alongside of BiCurass Ventilation (for respiratory support) 10
Experimental Group Leveteracitam high dose 60 mg/kg loading dose and 45mg/kg every 12 hours plus with biphasic cuirass ventilation for 3 days or until coma resolution (when the child is able to sit unsupported or breast feed if under 6 months). Prophylaxis Anticonvulsant treatment plus respiratory support 10
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Aged 3 months to 12-years 2. Hospitalised with: 2.1. Current or recent evidence of P. falciparum malaria (slide or rapid diagnostic test (RDT) positive) 2.2. Blantyre Coma Score 2 or less that persists even after correction for concurrent hypoglycaemia (defined as blood glucose <3 mmol/L) 2.3. History of seizures in this illness 1. Known cerebral palsy or significant neuro-development delay (which will affect endpoint assessment) 2. Skin disease or burns preventing use of the BCV 3. Respiratory or cardio-respiratory arrest prior to enrolment 4. A comorbidity which clinician believes has a significant risk of poor outcome e.g. malignancy, end-stage renal failure, major cardiac condition Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 3 Month(s) 12 Year(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
Yes 02/08/2018 Imperial College Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Norfolk Place London W2 1PG United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/07/2018 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
PO Box 5440 00200 Nairobi 54400020 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. Cumulative time with epileptogenic seizure activity will be determined by continuous EEG monitoring over 36 hours. Continuously, from time the child enrols into the study to 36 hours after enrolment
Secondary Outcome Feasibility will be assessed by ability to implement/operationalise the BCV for use on the high dependency ward in Kilifi County Hospital (assessed by whether this can generate negative pressure ventilation as per specification by the Hayek recommendations and averts respiratory safety endpoints). During the time when the child is receiving respiratory support with BCV. Measured by 1.The ability of BCV to safely institute negative pressure ventilation, which will be determined by resolution of
Secondary Outcome Safety Assessed by 1. Episodes of aspiration (determined by sudden decrease in oxygen saturations, and/or denovo presence of coarse chest crepitations, with evidence of gastric reflux/aspirate in the oropharynx). 2. Episodes of hypercarbia (defined as pCO2 level of greater than 45 mmHg). 3. Episodes of bradypnoea (defined as <10, 15 or 20 breaths/minute over 3 minutes for those aged <6m, 6-36m and >36m respectively) and hypoxaemia (oxygen saturation <92%). 4. Development of hypotension (defined as systolic blood pressure <50 mm Hg in children younger than 12 months; <60 mm Hg in children 1-5 years and <70 mm Hg in children olderthan 5 years of age). 5. Use of additional anticonvulsants. During the time when the child has BCV ventilation
Secondary Outcome Day 28 and day 180 mortality Day 20 and Day 180 post-enrolment
Secondary Outcome Neurocognative Sequelae Day 180 post enrolment
Secondary Outcome Re-admission to hospital through day 180 Day 180
Secondary Outcome Grade 3/4 adverse events through day 180 Up to Day 180
Secondary Outcome Length of initial hospitalisation At discharge from hospital
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kilifi Country Hospital Hospital Road Kilifi PO BOX230 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome 215 Euston Road London NW1 2BE United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Imperial College London Medical School Building, Norfolk Place London W2 1PG United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Mainga Hamaluba KEMRI Wellcome Trust, Hospital Road Kilifi POBox 230 Kenya
Nchafatso Obonyo KWTRP, Hospital Road Kilifi POBox 230 Kenya
Diana Gibb 90, High Holborn London WC1V 6LJ United Kingdom
A Sarah Walker 90 High Holborn London WC1V 6LJ United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kathryn Maitland k.maitland@imperial.ac.uk +254710508749 KWTRP, Hospital Road
City Postal code Country Position/Affiliation
Kilifi POBox230 Kenya Professor of Paediatrics
Role Name Email Phone Street address
Scientific Enquiries Emmanuel Oguda EOguda@kemri-wellcome.org +254726957045 KWTRP, Hospital Road
City Postal code Country Position/Affiliation
Kilifi POBox230 Kenya Trial Manager
Role Name Email Phone Street address
Public Enquiries Phyles Maitha PMaitha@kemri-wellcome.org +254735613157 KWTRP, Hospital Road
City Postal code Country Position/Affiliation
Kilifi POBox230 Kenya Trial administrator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The datasets used and/or analysed during the current study are available from the principal investigator on reasonable request. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol 6-months Requests for access to appropriately anonymized data from this trial can be made by application to the data access committee at the KEMRI-Wellcome Trust researchProgramme by e-mail toMMunene@kemri-wellcome.org
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