Investigation of the efficacy and safety of Suprotac® compared with Prograf® in liver transplant patients in Iran
Design
Randomized Clinical Trial; Two arms in parallel; Open-label; Phase 4 with 196 patients
Settings and conduct
Eligibles enter the study by signing informed consent. The intervention is performed on patients two months after transplantation (receiving Prograf in the first two months). The investigator assigns participants into two groups of Suprotac or Prograf, using a randomization series (1:1 allocation) according to the entry order. Patients in the suprotac group receive one milligram of Suprotac in exchange for each milligram of Prograf they have received pre-enrollment. The appropriate dose will be adjusted if needed to reach the desired trough level.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Patients aged between 18 to 70; two months past the liver transplantation
Exclusion criteria: Receiving any investigational products within the last 30 days; contraindication for tacrolimus; Experience of liver transplant rejection in the first two months after transplantation; Glomerular Filtration Rate greater than 30
Intervention groups
Intervention: Patients will receive Suprotac® (Nanoalvand Tacrolimus) from two months after transplantation surgery until one year after liver transplantation surgery, and the effectiveness and safety of this drug will be compared to the control group. Control: Patients will continue receiving Prograf® (Astellas Tacrolimus) from two months after transplantation surgery until one year after liver transplantation surgery.
Main outcome variables
Percentage of rejection-free patients between two groups (until one year after transplantation); Comparing the percentage of patient survival, graft survival, and mean trough concentration/dose of tacrolimus between two groups; Adverse events
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150303021315N25
Registration date:2021-09-13, 1400/06/22
Registration timing:registered_while_recruiting
Last update:2021-09-13, 1400/06/22
Update count:2
Registration date
2021-09-13, 1400/06/22
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-09-06, 1400/06/15
Expected recruitment end date
2023-09-06, 1402/06/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Open-label, randomized study to evaluate efficacy and safety of Suprotac® in comparison with Prograf® in liver transplant patients in Iran
Public title
Efficacy and safety evaluation of Suprotac® in comparison with Prograf® in prevention of liver transplant rejection
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Patient aged between 18 to 70 years
Patient who has passed two months from transplantation surgery
Patient who has received a stable dose of tacrolimus (prograf®) in the last 14 days before enrolment
Ability to comprehend and willing to sign the informed consent form for this study
Exclusion criteria:
Use of other investigational drugs at the time or within 30 days of enrolment, or within five half-lives of those drugs, whichever is longer (except for dialysis-related drugs which are not expected to interact with the study regimens)
Patients with contraindication for tacrolimus or any other ingredients of the formulation
Patients who underwent liver transplant rejection in the first two months after liver transplantation
Patients with Glomerular Filtration Rate greater than 30 at the time of enrolment to the study (two months after liver transplantation)
Age
From 18 years old to 70 years old
Gender
Both
Phase
4
Groups that have been masked
No information
Sample size
Target sample size:
196
Randomization (investigator's opinion)
Randomized
Randomization description
Eligible patients will be assigned to treatment using stratified block randomization with blocks of size 2 or 4. Randomization will be stratified according to living or deceased donors. The patients will be carried out using R-CRAN software version 3.6.3. Blocks will be made using permuted block randomization for a total of 196 patients (1:1 allocation ratio). The random series Excel will be placed in the patient recruitment center and a person will be responsible for assigning a random code by the investigator. This code will be assigned in order of entry and based on the stratification in which the patient's donor is living or deceased.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committees of Shiraz University of Medical Sciences
Street address
Zand Street
City
Shiraz
Province
Fars
Postal code
7134814336
Approval date
2021-07-03, 1400/04/12
Ethics committee reference number
IR.SUMS.REC.1400.308
Health conditions studied
1
Description of health condition studied
Liver transplant
ICD-10 code
Z94.4
ICD-10 code description
Liver transplant status
Primary outcomes
1
Description
Transplantation rejection
Timepoint
All along the study duration until one year after transplantation surgery
Method of measurement
Liver transplant rejection approved by biopsy or clinical symptoms and laboratory tests (enhancement in alanine aminotransferase or aspartate aminotransferase liver enzymes)
Secondary outcomes
1
Description
Death
Timepoint
All along the study duration until one year after transplantation surgery
Method of measurement
Incidence of death written in the adverse event’s section of the case report form
2
Description
Graft loss
Timepoint
All along the study duration until one year after transplantation surgery
Method of measurement
Transplant rejection not responsive to the treatment according to the biopsy or clinical symptoms and laboratory tests (enhancement in alanine aminotransferase or aspartate aminotransferase liver enzymes)
3
Description
Mean trough concentration per dose of tacrolimus
Timepoint
Baseline, months 2, 4, 6 and 10
Method of measurement
Dividing trough concentration to the consumed daily dose
4
Description
Adverse events
Timepoint
Baseline, months 2, 4, 6 and 10
Method of measurement
All adverse events are assessed through patient reporting, physician diagnosis, or laboratory abnormalities, and are then classified by severity (based on Common Terminology Criteria for Adverse Events (CTCAE)), seriousness, relationship to the study drug, action taken, and outcome.
Intervention groups
1
Description
Intervention group: Patients will receive Suprotac® (Tacrolimus produced by Nano Alvand Co.) with mycophenolic acid and prednisolone until one year after liver transplantation surgery. Suprotac® dose in these patients will be equivalent to dose they’ve received of prograf® (Tacrolimus produced by Astellas Pharma) before enrolment (two months after transplantation surgery) which had been adjusted to achieve target trough concentration of tacrolimus. Daily dose of Suprotac® will be administered in two divided doses, given every 12 hours.
Category
Treatment - Drugs
2
Description
Control group: Patients will continue receiving Prograf® (Tacrolimus produced by Astellas Pharma) with mycophenolic acid and prednisolone until one year after liver transplantation surgery. Daily dose of Prograf® which has been adjusted to achieve target trough concentration will be administered in two divided doses, given every 12 hours.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Abu-Ali Sina Hospital
Full name of responsible person
Dr Saman Nik-Eghbalian
Street address
2nd Phase, Sadra
City
Shiraz
Province
Fars
Postal code
7199467985
Phone
+98 71 3344 0000
Email
Nikeghbalian@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Nanoalvand Company
Full name of responsible person
Dr Nima Sepehri
Street address
No. 485, between 63th and 65th Ave., Yousef Abad
City
Tehran
Province
Tehran
Postal code
1439955991
Phone
+98 21 8802 0579
Email
info@nanoalvand.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Nanoalvand Company
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry
Person responsible for general inquiries
Contact
Name of organization / entity
Orchid Pharmed
Full name of responsible person
Nassim Anjidani
Position
Medical Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Attar Neyshaboori St., Vanak Sq., Tehran
City
Tehran
Province
Tehran
Postal code
1994766411
Phone
+98 21 4347 3000
Fax
Email
anjidani.n@orchidpharmed.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Orchid Pharmed
Full name of responsible person
Nassim Anjidani
Position
Medical Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Attar Neyshaboori St., Vanak Sq., Tehran
City
Tehran
Province
Tehran
Postal code
1994766411
Phone
+98 21 4347 3000
Fax
Email
anjidani.n@orchidpharmed.com
Person responsible for updating data
Contact
Name of organization / entity
Orchid Pharmed
Full name of responsible person
Nassim Anjidani
Position
Medical Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Attar Neyshaboori St., Vanak Sq., Tehran
City
Tehran
Province
Tehran
Postal code
1994766411
Phone
+98 21 4347 3000
Fax
Email
anjidani.n@orchidpharmed.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available