Mannitol Use During Cadaveric Kidney Transplantation

January 17, 2021 updated by: Rabin Medical Center

A Prospective, Randomized, Double Blinded, Placebo Control Trial to Evaluate Efficacy of Intravenous Mannitol Use During Cadaveric Kidney Transplantation Prior to Kidney Reperfusion

We propose a placebo controlled randomized study on the use of mannitol as an agent to protect against delayed graft function, during the surgical procedure of kidney transplantation from a cadaver. Patients undergoing kidney transplantation for the treatment of end stage kidney disease will be randomized in a ratio of 1:1 to receive either intravenous mannitol or saline during their procedure, administered prior to renal artery clamp release and reperfusion of the kidney. Changes in renal function following surgery and the incidence and duration of delayed graft function (DGF) will be monitored using calculated glomerular filtration rate (eGFR) and the need for dialysis performed post-operatively, as part of routine standard of care. Additionally biological samples will be collected and analyzed for use of a non invasive biomarker for delayed graft function.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a prospective randomized double-blind placebo-controlled trial comparing renal function outcomes in patients undergoing cadaver donor renal transplant for end stage kidney failure. Patients will be randomized to receive 0.5 g / kg body weight, of mannitol or saline 0.9% as an intravenous infusion to be initiated and be completely infused within 15-30 minutes prior to vascular clamp removal of the transplanted renal artery.

Prior to surgery, all study participants will receive standard departmental treatment as all other patients undergoing a kidney transplantation from a cadaver.

Upon arrival to the operating room patients will be placed supine on the operating room table, and will be connected to an anesthesia monitor which will include monitoring the HR, blood pressure, saturation, temperature and ECG as standard departmental procedure. After connecting the participant to the anesthesia monitor an IV line will be inserted, as is standard clinical practice. In addition, venous central line catheter for central venous pressure monitoring and specific inotropic drugs infusion, as well as arterial line catheter for blood pressure monitoring, will be initialized upon anesthesiologist team decision The technique of kidney transplantation is well-standardized . None of the techniques utilized in the study are considered experimental and all are considered standard therapeutic options for a patient undergoing cadaveric donor kidney transplantation. The procedures are performed under general anesthesia with non-invasive intraoperative vital sign monitoring, as is standard departmental practice. Study participation will not affect anesthesia method or protocol treatment in anyway.

Upon study enrollment patients will be randomized in 1:1 ratio for study arm treatment/control. The perioperative team, investigator and patient will be blinded to the intervention.

Study arm: Patients randomized to receive the treatment arm will receive 0.5 g / kg body weight of mannitol. The mannitol solution used in the hospital contain 18% mannitol in 500ml solution. An equivocal volume of 2.8 cc / kg body weight, which will be given intravenously with the use of an Ivac pump, infused for a duration of 15 minutes through an existing peripheral intravenous access catheter within 15-30 minutes prior to renal artery reperfusion.

The placebo arm (Control arm) Study participants randomized to this arm will receive a 0.9% saline solution at a dose of 2.8 cc / kg, infused within 15-30 minutes prior to renal artery reperfusion through an existing intravenous access catheter (either through an central or peripheral intravenous infusion).

Following receiving the study drug, either mannitol or saline, patients will receive 80 mg furosemide, which will be given intravenously.

Fluid management throughout the kidney transplant surgery for all study participants will consist as follows:

  • Upon arrival to the operating room, immediately following IV insertion, all patients will receive an IV infusion of Plasma-Lyte as it is a standard protocol at our institute for kidney transplant surgery.
  • After induction of anesthesia, the patient will receive Plasma-Lyte solution at a rate of 8 cc / kg body weight per hour.
  • At this stage of the procedure, before reperfusion of the transplanted kidney, the purpose of this fluid management is intended to maintain a minimum systolic blood pressure of 90-100mmHg.
  • At 30 to 15 minutes before reperfusion, in purpose to let the transplanted kidney get better opening conditions, the target blood pressure is elevated to an mean arterial pressure (MAP) of not less than 100 mmHg. In order to achieve that, additional 1000 cc of Plasma-Lyte will be given to the patient 30 to 15 minutes before re-perfusion. In addition, small boluses (each 0.1 mg) of Phenylephrine will be given as needed to maintain that MAP.
  • Thereafter, and until the end of the operation, the fluid management will be titrated according to the patient's blood pressure, ensuring that systolic blood pressure does not fall below 120 mmHG, as the common departmental protocol in such surgeries. In occasions of hypotension, a bolus of 250 cc Plasma-Lyte will be given to increase the blood pressure.
  • If there is insufficient response to repeat boluses, vasopressors (phenylephrine, ephedrine or noradrenaline) will be given at the discretion of the anesthesiologist.
  • Episodes of hypotension not responsive to intravenous fluids will be treated with intravenous vasopressors (phenylephrine, ephedrine or noradrenaline as needed) at the discretion of the anesthesiologist. The provision of these drugs will be documented individually in the study report for each patient, as is common clinical practice.
  • After surgery, in the post anesthesia care unit (PACU), the patient will receive 80 cc / hour of Plasma-Lyte or 120% of urine output if urine output exceeds 80 cc. Patients are regularly supervised in PACU for 2-4 hours after the end of the operation and then transferred to the department of organ transplantation. In cases of need for dialysis or prolonged ventilation, they stay at PACU.
  • The fluid management for the postoperative days are as standard regimen in our center which consists of giving the patient full fluid replacement at POD1 - including urine output and drains output. On the next post-operative days, we replace 80% of urine output in IV fluids and oral intake together.

Additionally blood and urine samples maybe collected from some of the patients (In the event that it is possible) at the following different timelines:

Immediately before administering mannitol Immediately after administering mannitol 24 hours after transplant 7 days after transplant, These biological samples will be collected and analyzed to asses the presence of proteins, exosomes , cytokines that can be used as a non invasive biomarker for delayed graft function.

Study Type

Interventional

Enrollment (Anticipated)

32

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age >18 years
  • Patients on the list of cadaveric donor kidney transplantation

Exclusion Criteria:

  • Allergy to mannitol
  • Allergy to furosemide
  • Combined major surgical cases that may include transplantation of another organ on the same time, such as liver.
  • Severe congestive heart failure (ejection fraction < 30%)
  • Patients with coagulation disorders.
  • Patients who are not able to sign an informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients randomized to receive the treatment arm of mannitol.
The mannitol solution used in the hospital contain 18% mannitol in 500ml solution. An equivocal volume of 2.8 cc / kg body weight, which will be given intravenously with the use of an Ivac pump, infused for a duration of 15 minutes through an existing peripheral intravenous access catheter within 15-30 minutes prior to renal artery reperfusion
Drug: Mannitol

Mannitol (Israeli Brand Name: Osmitrol) is in the osmotic diuretic pharmacologic categoryaccording to the American Hospital Formulary Service (AHFS) database. . During the procedure, volume of 2.8 cc / kg body weight of the solution bag (either mannitol or saline 0.9%) will be given. The bag itself will be covered so it cannot be identified which solution is in it and marked per patient.

Mannitol is injected by intravenous infusion using an I-vac pump and infused over 15 minutes.
Placebo Comparator: (Control arm) Study participants will receive a 0.9% saline solution
(Control arm) Study participants randomized to this arm will receive a 0.9% saline solution at a dose of 2.8 cc / kg, infused within 15-30 minutes prior to renal artery reperfusion through an existing intravenous access catheter (either through an central or peripheral intravenous infusion).
Drug: Saline
Study participants randomized to this arm will receive a 0.9% saline solution at a dose of 2.8 cc / kg, infused within 15-30 minutes prior to renal artery reperfusion through an existing intravenous access catheter (either through an central or peripheral intravenous infusion).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dialysis after surgery
Time Frame: within 7 days postoperatively
within 7 days postoperatively
Urine Output ml per day
Time Frame: Within 7 days postoperatively.
Within 7 days postoperatively.
Creatinine value
Time Frame: All 7 days postoperatively
All 7 days postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rabin Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 1, 2022

Primary Completion (Anticipated)

February 1, 2022

Study Completion (Anticipated)

February 1, 2022

Study Registration Dates

First Submitted

January 10, 2021

First Submitted That Met QC Criteria

January 10, 2021

First Posted (Actual)

January 12, 2021

Study Record Updates

Last Update Posted (Actual)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 17, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0826-20-RMC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Renal Dialysis

Clinical Trials on Mannitol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Montenegro

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe