| CTRI Number |
CTRI/2024/09/073282 [Registered on: 03/09/2024] Trial Registered Prospectively |
| Last Modified On: |
02/09/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Effect of Ceftazidime avibactam renal dose adjustment in first the 48hrs |
|
Scientific Title of Study
|
Ceftazidime-avibactam with or without renal modification in first 48 hours in patients with sepsis and acute kidney injury (CAR SAKI): An Open-Label Randomized Controlled Trial |
| Trial Acronym |
CAR SAKI |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Haripriya Reddy Challa |
| Designation |
Consultant, Department of Infectious Diseases |
| Affiliation |
AIG Hospitals |
| Address |
Department of Infectious diseases, 7th floor Tower B, Survey No 136, 4/5, Plot No 2/3, Mindspace Rd, P Janardhan Reddy Nagar, Gachibowli, Hyderabad
Hyderabad
TELANGANA
500032
India |
| Phone |
|
| Fax |
|
| Email |
dr.haripriyareddy@aighospitals.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ankit Mittal |
| Designation |
Consultant, Department of Infectious Diseases |
| Affiliation |
AIG Hospitals |
| Address |
Department of Infectious diseases, 7th floor Tower B, Survey No 136, 4/5, Plot No 2/3, Mindspace Rd, P Janardhan Reddy Nagar, Gachibowli, Hyderabad
Hyderabad
TELANGANA
500032
India |
| Phone |
9051904948 |
| Fax |
|
| Email |
dr.ankitmittal@aighospitals.com |
|
Details of Contact Person
Public Query
|
| Name |
Racha Amarthya sree |
| Designation |
Clinical research coordinator |
| Affiliation |
AIG Hospitals |
| Address |
Department of critical care, Tower A 3rd floor, ICU 2, Survey No 136, 4/5, Plot No 2/3, Mindspace Rd, P Janardhan Reddy Nagar, Gachibowli, Hyderabad
Hyderabad
TELANGANA
500032
India |
| Phone |
7093884317 |
| Fax |
|
| Email |
rasree07@gmail.com |
|
|
Source of Monetary or Material Support
|
| Glenmark Pharmaceuticals Limited (Material support),Glenmark House, B. D. Sawant Marg, Chakala, Off Western Express Highway, Andheri (E), Mumbai – 400 099. |
|
|
Primary Sponsor
|
| Name |
Glenmark Pharmaceuticals Limited |
| Address |
Glenmark House, B.D. Sawant Marg, Parshiwada, Chakala, Andheri East, Mumbai, Maharashtra 400099 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Haripriya Reddy Challa |
AIG Hospitals |
Tower B 7th floor, Department of Infectious Diseases, Survey No 136, 4/5, Plot No 2/3, Mindspace Rd, P Janardhan Reddy Nagar, Gachibowli, Hyderabad
Hyderabad
TELANGANA |
7893113303
dr.haripriyareddy@aighospitals.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee Asian Institute of Gastroenterology |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: A415||Sepsis due to other Gram-negativeorganisms, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Ceftazidime avibactam 2.5g only one dose |
After first full dose (2.5g), dose will be modified according to renal function as estimated by Cockroft gault equation |
| Intervention |
Ceftazidime-avibactam 2.5g every 8hrly |
Drug will be administered every 8hrly for first 48 hrs and further doses will be modified based on renal function estimated using Cockroft gault equation. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
a. Patients diagnosed with Sepsis
b. Patients with Acute kidney injury according to KDIGO criteria.
c. The patient or approved proxy is able to provide informed consent.
|
|
| ExclusionCriteria |
| Details |
a. Treatment is not with the intent to cure the infection (that is, palliative care is an exclusion).
b. Patients with Chronic kidney disease on dialysis
c. Pregnancy or breast-feeding.
d. Use of study drug within last 7 days before recruitment in the study
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| All-cause mortality rate will be measured as the number of deaths on or before 28 days after inclusion in the study. |
On day 28 after inclusion in the study, the primary outcome will be measured as stated above. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Clinical cure is defined as a patient is alive, with resolution or substantial improvement of baseline signs & symptoms (defervescence), & a delta sequential organ function assessment (ΔSOFA) score of less than 2, with or without microbiological cure, & no requirement of rescue antibiotic therapy. |
Clinical cure will be measured on Day 14 & 28 of inclusion. |
|
|
Target Sample Size
|
Total Sample Size="108"
Sample Size from India="108"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 4 |
|
Date of First Enrollment (India)
|
15/09/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Ceftazidime avibactam has become a widely utilized antibiotic in the management of Carbapenem resistant gram-negative bacterial sepsis. The early and appropriate management of sepsis is crucial to prevent the development of septic shock with multi-organ failure, which can result in increased mortality. Ceftazidime avibactam is primarily eliminated by the kidneys and has a wide therapeutic index, with relatively few safety concerns when administered at the maximum dose, as compared to other antimicrobial classes. However, the data on the dosing strategy in AKI patients within the first 48 hours of sepsis and its impact on outcomes is inconclusive. Thus, we hypothesized that dose adjustment could be deferred until 48 hours after initiation of therapy. The aim of renal dosage adjustments is to achieve equivalent exposures in patients with and without renal impairment, thereby minimizing toxicity without compromising efficacy. However, a recent meta-analysis showed that, compared to subjects receiving the full dose of ceftazidime-avibactam, those undergoing renal dose modifications had almost a two-fold increased risk of mortality. Such a deferred dose adjustment strategy could be employed in clinical trials and practice to ensure pharmacodynamic targets are met during this critical period in therapy. The study will provide clarity on adequate early antibiotic therapy with ceftazidime avibactam by optimizing the pharmacokinetic-pharmacodynamic targets, a primary driver of outcomes, thus justifying the need for the study. |