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.: PACTR202203622900599 Date of Approval: 23/03/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Mannitol for acute kidney injury during liver transplantation
Official scientific title Mannitol for prevention of Acute Kidney Injury during living donor Liver Transplantation: A Randomized Controlled Trial
Brief summary describing the background and objectives of the trial Liver transplantation becomes the standard treatment of end-stage liver disease and selected cases of liver neoplasms.1 Due to Ischemia-reperfusion injury (IRI), Acute kidney injury (AKI) reaches up to 95% in the liver transplantation setting. During graft ischemia, the degradation of ATP molecules results in the accumulation of hypoxanthine. After reperfusion and reoxygenation of the graft, hypoxanthine produces toxic reactive oxygen species (ROSs) by xanthine oxidase.2,3 ROS produce cellular injury by lipid peroxidation of the cell membranes, leukocyte activation, chemotaxis, and leukocytes-endothelial adhesion. Superoxide dismutase, N-acetyl cysteine, mannitol, vitamin E, vitamin C, and allopurinol are common examples of antioxidants.5 On the histopathological and biochemical levels, mannitol and ascorbic acid were effective in scavenging and inhibiting ROS after liver IRI.6 Additionally, mannitol creates a hyperosmolar environment, which may blunt the IRI.7 Mannitol attenuated renal injury after pancreas IRI in an animal study. During living donor kidney transplantation, mannitol drip within 15 minutes of cross-clamping enhances renal preservation. While in liver transplantation, mannitol infusion during the an-hepatic phase could ameliorate PRS.mIn contrast, Whitta et al. found no protective effect of mannitol on kidney function during liver transplantation. Nonetheless, they only studied 25 patients and infused mannitol immediately after induction. Given this contradictory evidence, we hypothesized that using mannitol during the an-hepatic phase in LDLT would decrease the incidence of early AKI. The present study aimed to investigate the effects of mannitol on AKI, post-reperfusion syndrome, and graft function after LDLT.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Kidney Disease
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention
Anticipated trial start date 15/11/2017
Actual trial start date 10/12/2017
Anticipated date of last follow up 22/10/2019
Actual Last follow-up date 22/10/2019
Anticipated target sample size (number of participants) 84
Actual target sample size (number of participants) 80
Recruitment status Completed
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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Mannitol infusion on the start of warm ischemia a single dose of 1 g/kg mannitol 20% on the start of the warm ischemia. infused over 20 minutes At the start of warm ischemia, the envelope was opened, and a single dose of 1 g/kg mannitol 20% was infused over 20 minutes. The right hepatic vein was unclamped then the portal vein and the graft preservative contents were washed into the systemic circulation by the portal blood. 41
Control Group Saline The same volume of the corresponding Mannitol dose of 1 g/kg mannitol 20% over 20 minutes At the start of warm ischemia, the envelope was opened, and saline (control) was infused over 20 minutes. The right hepatic vein was unclamped then the portal vein and the graft preservative contents were washed into the systemic circulation by the portal blood. 39 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Adult (‚Č• 18 years old) patients 2. Either sex 3. Undergoing living donor liver transplantation with right lobe graft from family-related donors. 1. Acute fulminant hepatitis 2. Estimated Graft/Recipient Weight ratio (GRWR) < 0.8 3. Portal hypertension with mean pulmonary blood pressure > 35 mmHg 4. Preoperative serum creatinine (SCr) > 1.4 mg/dl or dialysis within the last 3 months 5. Diabetes Mellitus (> 10 years) 6. Preoperative serum sodium [Na+] < 125 mEq/L and serum potassium [K+] > 5.5 mEq/L 7. Intra-operative massive blood transfusion (replacement of > 50% of total blood volume in < 3 hours) Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 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 25/08/2017 IRB Mansoura University Faculty of Medine
Ethics Committee Address
Street address City Postal code Country
Elgomhoria Mansoura 35516 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Early acute kidney injury, defined as 0.3 mg/dl of SCr increase from the baseline in the early 48 post¬operative hours or 50% increase in the S. Cr within 48 hours. 48 hours after transplantation
Secondary Outcome All-cause mortality 3 months after transplantation
Secondary Outcome Intensive Care length of stay till discharge from the ICU
Secondary Outcome intraoperative CI, SVI, MAP, MPAP, CVP, PAOP, SVR, PVR, and serum [Na+], [K+], ionized [Ca2+], and [Cl-] at 6 intraoperative times - (1) immediately before skin incision, (2) the beginning of the an-hepatic (portal vein clamping), (3) 5 minutes before portal reperfusion (basal), (4) at 5 min after portal unclamping, (5) 5 minutes a 6 intraoperative time points
Secondary Outcome liver graft function 3 months after transplantation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Mansoura University Gastrointestinal Surgery Center Gehan st Mansoura 35516 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Self funded Elgomhoria Mansoura 35611 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Mansoura University Elgomhouria Mansoura 35516 Egypt University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Moataz Maher Emara mm.emara@mans.edu.eg 0201064048848 Gehan
City Postal code Country Position/Affiliation
Mansoura 35516 Egypt Clinical Lecturer of Anaesthesiology and Intensive Care at Mansoura University Faculty of Medicine
Role Name Email Phone Street address
Scientific Enquiries Amr Yassen amryassen@hotmail.com 0201001497044 Gehan
City Postal code Country Position/Affiliation
Mansoura 35516 Egypt Professor of Ansesthsiology and Intensive Care at Mansoura University Faculty of Medicine
Role Name Email Phone Street address
Public Enquiries Moataz Maher Emara mm.emara@mans.edu.eg 0201064048848 Gehan
City Postal code Country Position/Affiliation
Mansoura 35516 Egypt Clinical Lecturer of Anaesthesiology and Intensive Care at Mansoura University Faculty of Medicine
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The Anonymous patient data will be available with the PI or the corresponding author on reasonable request according to the local IRB regulations. Informed Consent Form,Statistical Analysis Plan,Study Protocol Will be available after publication with the PI or the corresponding author on reasonable request according to the local IRB regulations. on reasonable request according to the local IRB regulations.
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
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 12/03/2022 It was only a typo. We have 41 participants in the intervention group and 39 in the control group, so the total is 80 cases. Experimental Group, Mannitol infusion on the start of warm ischemia, a single dose of 1 g/kg mannitol 20% on the start of the warm ischemia., infused over 20 minutes, At the start of warm ischemia, the envelope was opened, and a single dose of 1 g/kg mannitol 20% was infused over 20 minutes. The right hepatic vein was unclamped then the portal vein and the graft preservative contents were washed into the systemic circulation by the portal blood., 41,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/03/2022 I had some time to re-extract the approval letter from the IRB body. TRUE, IRB Mansoura University Faculty of Medine, Elgomhoria, Mansoura, 35516, Egypt, , 25 Aug 2017, 020502383781, irb@mans.edu.eg, TRUE, IRB Mansoura University Faculty of Medine, Elgomhoria, Mansoura, 35516, Egypt, , 25 Aug 2017, 020502383781, irb@mans.edu.eg, 21511_17003_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 21/03/2022 The investigators did not receive a specific fund for this research, so we initially choose that we did not receive fund till the reviewer comment to change to "Self-Funded". Self funded, Elgomhoria, Mansoura, 35611, Egypt, Hospital,