| CTRI Number |
CTRI/2024/12/077751 [Registered on: 06/12/2024] Trial Registered Prospectively |
| Last Modified On: |
03/12/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Observational |
|
Type of Study
|
Retrospective |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A Study to find the importance of genotyping in tacrolimus dose in kidney transplant patients |
|
Scientific Title of Study
|
Precise Tacrolimus Dose Adjustments in Kidney Transplant patients from Industrial Workforce Considering CYP3A5 Genotyping Beyond Therapeutic Drug Monitoring |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Imran Ahmed Siddiqui |
| Designation |
Professor |
| Affiliation |
ESIC Medical College and Super Specialty Hospital |
| Address |
Room no. 102, Laboratory services, ESI Super Specialty Hospital, Sanathnagar
Hyderabad
TELANGANA
500038
India |
| Phone |
9666913786 |
| Fax |
|
| Email |
write2drimran@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Imran Ahmed Siddiqui |
| Designation |
Professor |
| Affiliation |
ESIC Medical College and Super Specialty Hospital |
| Address |
Room no. 102, Laboratory services, ESI Super Specialty Hospital, Sanathnagar
Hyderabad
TELANGANA
500038
India |
| Phone |
9666913786 |
| Fax |
|
| Email |
write2drimran@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Imran Ahmed Siddiqui |
| Designation |
Professor |
| Affiliation |
ESIC Medical College and Super Specialty Hospital |
| Address |
Room no. 102, Laboratory services, ESI Super Specialty Hospital, Sanathnagar
Hyderabad
TELANGANA
500034
India |
| Phone |
9666913786 |
| Fax |
|
| Email |
write2drimran@gmail.com |
|
|
Source of Monetary or Material Support
|
| ESIC Medical College and Super Specialty Hospital, Sanathnagar, Hyderabad, Telangana, India - 500038 |
|
|
Primary Sponsor
|
| Name |
Imran Ahmed Siddiqui |
| Address |
Room no. 102, Laboratory services, ESI Super Specialty Hospital, Sanathnagar, Hyderabad, Telangana, India - 500038 |
| Type of Sponsor |
Other [self] |
|
|
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 Imran Ahmed Siddiqui |
ESIC Medical College and Super Specialty Hospital |
Department of Biochemistry and Pharmacology, Room no. 1001, Sanathnagar, Hyderabad
Hyderabad
TELANGANA |
966613786
write2drimran@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committe ESIC Medical College & Hospital and ESIC Super Specialty Hospital |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N186||End stage renal disease, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
NIL |
NIL |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. ESIC Insured Patients who underwent kidney transplantation between Dec 2022 to April 2024
2. Received Kidney from live or cadaveric donors
3. Prescribed tacrolimus as immunosuprresant |
|
| ExclusionCriteria |
| Details |
1. ESIC Insured patients who underwent any transplantation other than kidney
2. ESIC Insured patients from non-industrial workforce |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
|
|
Blinding/Masking
|
|
|
Primary Outcome
|
| Outcome |
TimePoints |
| Patients achieving target tacrolimus trough concentrations 7-10ng/ml |
day 6, 3rd month, 6th month |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. To estimate the incidence of New Onset Diabetes Mellitus After Transplantation (NODAT)
2. Rejection episodes
3. Graft function |
1. at 6th month
2. in 6 months
3. Day 6, 3rd month and 6th month |
|
|
Target Sample Size
|
Total Sample Size="16"
Sample Size from India="16"
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
|
N/A |
|
Date of First Enrollment (India)
|
16/12/2024 |
| 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="0"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| 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
|
The average bioavailability of Tacrolimus is merely 25%and it varies, ranging from 5 to 90% [5]. About 99% of Tacrolimus binds to erythrocytes after entering the systemic circulation [5]. It is primarily metabolized by the CYP3A enzyme system, which includes CYP3A5, CYP3A4, CYP3A7. and CYP3A43 which is expressed in small intestine, liver and kidney [5]. Compared with CYP3A5, the catalytic efficiency of CYP3A4 was relatively low [5]. The CYP3A7 has little influence on the metabolism of Tacrolimus, while the role of CYP3A43 is unclear [5]. The total body clearance of Tacrolimus is relatively low, around 0.06 L/(hâ‹…kg) [5]-. The half-life is long and variable, ranging from 4 to 41 h (about 12 h on average) [5]. Approximately 95% of Tac metabolites are excreted by bile, and urinary excretion is only about 2% [5]. Only 0.5% of the original drug is excreted through urine and feces [5]. Polymorphisms of cytochrome P450 3A5 (CYP3A5) enzyme significantly affects tacrolimus metabolism [6]. The most notable alleles are CYP3A5 *1/*1 (Extensive metabolizer) or *1/*3 alleles (Intermediate metabolizer), which result in the expression of functional CYP3A5 and lead to higher tacrolimus clearance [6]. Patients with these alleles require higher doses of tacrolimus to achieve therapeutic drug levels compared to individuals with the CYP3A5 *3/*3 genotype (poor metabolizer), who are non-expressers of the enzyme and thus have reduced clearance [6]. Despite its efficacy, the clinical management of tacrolimus is challenging due to its narrow therapeutic index [7]. There is significant inter and intra-patient variability in pharmacokinetics and pharmacodynamics [7]. The attributable factors are age, weight, organ function, co-medications and genetic polymorphisms on drug-metabolizing enzymes and transporters [7]. Given these complexities, Therapeutic Drug Monitoring (TDM) of tacrolimus is essential to ensure that optimal blood concentrations remain within the therapeutic range, thus minimizing the risks of rejection and toxicity [8]. The study integrating dual monitoring with genotype and TDM are already available for the dosage adjustment which enhances the precision of dosing regimens. But such combined studies in patients from Industrial workforce are shortly reported. |