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.: PACTR202009811610400 Date of Approval: 16/09/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Continuous vs. intermittent beta-lactam dosing in critically ill patients with sepsis: A randomized controlled trial.
Official scientific title Continuous vs. intermittent beta-lactam dosing in critically ill patients with sepsis: A randomized controlled trial.
Brief summary describing the background and objectives of the trial A prospective, randomized controlled trial including 408 patients aged one month or older, with sepsis being treated with beta lactam antibiotics, will be undertaken in the Chris Hani Baragwanath Academic Hospital’s (CHBAH) main intensive care unit (ICU). Patients will be screened and if deemed eligible, will be enrolled into the study after obtaining informed consent. Demographic data and baseline characteristics will be recorded and patients will be randomized into either the standard therapy group (to receive antibiotics as per usual care which is intermittent bolus doses) or the continuous infusion therapy group. Blood samples will be obtained on day 3 post randomization, to determine antibiotic time of free drug concentration above minimum inhibitory concentration (fT > MIC). Patients records will then be reviewed on day 14 post randomization to obtain data to determine clinical cure rates, type of infection, including acquisition of new infection or colonization while being treated for initial infection, number of days requiring organ support and number of days to normalization of white cell count. Patients or their next of kin shall be contacted on day 28 and again day 90 to determine ICU, 28 day and 90 day mortality rates. The data for each group will be compared using appropriate statistical analysis tests.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Sepsis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 21/09/2020
Actual trial start date
Anticipated date of last follow up 24/12/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 408
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 Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Continuous infusion of beta lactam antibiotic Dose determined by treating doctor Dose for 24 hours run continuously over the 24 hour pwriod Determined by treating doctor To compare clinical cure rates in the two groups - continuous infusion of beta lactam antibiotic & intermittent bolus of beta lactam antibiotic (standard care). To determine if continuous infusion of beta lactam antibiotics achieves a better pharmacokinetic profile, to be determined by checking the duration that the blood levels of the antibiotic remain above MIC 204
Control Group Intermittent bolus of beta lactam antibiotic As per treating doctor As per treating doctor To determine clinical cure rates compared with continuous infusion group To determine the duration that antibiotic levels remain above minimum inhibitory concentration (MIC) 204 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
All patients, adult and paediatric, admitted to the intensive care unit with sepsis Prescription of one of four beta lactam antibiotics by treating doctor: 1. Amoxicillin- clavulanate 2. Piperacillin-tazobactam 3. Meropenem 4. Imipenem Anticipated ICU at least 48 hours. Pregnancy Less than 1 month old Chronic renal failure (eGFR<30ml/min) Patient admitted and already on renal replacement therapy Inadequate intravenous access Infections in which standard recommended antibiotic duration is > 14 days (eg: infective endocarditis, osteomyelitis) Patients receiving palliative care at study assessment Patient previously enrolled on this study Declined consent 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 1 Month(s) 100 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 21/10/2019 Human Research Ethics Committee Medical
Ethics Committee Address
Street address City Postal code Country
29 Princess of Wales Terrace, Parktown, Johannesburg Parktown 2193 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Adults - To compare the clinical cure rates at day 14 (D14) post randomization to the antibiotic strategy 14 days post randomization
Primary Outcome Paediatrics - To determine the proportion of patients in the IB group with an expected time above minimum inhibitory concentration (MIC) of less than 100% day 3 post randomization
Secondary Outcome To compare the 2 groups with respect to the following in both adult and paediatric groups 1. The time above minimum inhibitory concentration in the 2 groups on day 3 2. Duration of antibiotics between the 2 groups 3. Normalization of an abnormal white cell count 4. Colonization or infection with new organisms 5. Duration of ventilation 6. Duration of vasopressor support 7. Duration of (RRT) renal replacement 8. ICU length of stay (LOS) 9. ICU mortality 10. Day 28/hospital discharge mortality 11. Day 90 mortality 12. Paediatrics clinical cure rates at day 14 (D14) post randomization to the antibiotic strategy. Day 3, Day 14 or ICU discharge, Day 28 or hospital discharge and Day 90
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Chris Hani Baragwanath Academic Hospital Chris Hani Road Soweto 2013 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Shahed Omar 26 Chris Hani Road Soweto 2013 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Applied for and awaiting approval Unit 29 Honeydew Shopping Centre Cnr Beyers Naude and Blueberry Street Johannesburg 2040 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Jaya George 17 Jubilee Road Johannesburg 2193 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ayesha Khan Ayesha.Khan@wits.ac.za +27825503102 26 Chris Hani Road
City Postal code Country Position/Affiliation
Johannesburg 1864 South Africa Paediatric intensivist
Role Name Email Phone Street address
Scientific Enquiries Shahed Omar shahedicu@gmail.com +27835695363 26 Chris Hani Road
City Postal code Country Position/Affiliation
Johannesburg 1864 South Africa Intensivist
Role Name Email Phone Street address
Public Enquiries Shahed Omar shahedicu@gmail.com +27835695363 26 Chris Hani Road
City Postal code Country Position/Affiliation
Johannesburg 1864 South Africa Head of Research
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All of the individual participant data collected during the trial, after de-identification Study Protocol Immediately following publication, and ending 5 years following article publication Researchers who provide a methodologically sound proposal To achieve aims in the approved proposal Proposal should be directed to Ayesha.Khan@wits.ac.za. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be included)
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