Mannitol Use During Cadaveric Kidney Transplantation

NCT04705402 | Unknown DMC

• 1 other identifier: 0826-20-RMC
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Renal Dialysis

Outcome Measures

Primary Outcomes (3)

• Incidence of dialysis after surgery

  within 7 days postoperatively

• Urine Output ml per day

  Within 7 days postoperatively.

• Creatinine value

  All 7 days postoperatively

Study Arms (2)

Patients randomized to receive the treatment arm of mannitol.

EXPERIMENTAL

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

(Control arm) Study participants will receive a 0.9% saline solution

PLACEBO COMPARATOR

(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

Interventions

Mannitol DRUG

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.

Patients randomized to receive the treatment arm of mannitol.

Saline DRUG

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).

(Control arm) Study participants will receive a 0.9% saline solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rabin Medical Center: lead

Related Publications (15)

• Lugo-Baruqui JA, Ayyathurai R, Sriram A, Pragatheeshwar KD. Use of Mannitol for Ischemia Reperfusion Injury in Kidney Transplant and Partial Nephrectomies-Review of Literature. Curr Urol Rep. 2019 Jan 26;20(1):6. doi: 10.1007/s11934-019-0868-6.

  PMID: 30685826 BACKGROUND

• Gagandeep S, Matsuoka L, Mateo R, Cho YW, Genyk Y, Sher L, Cicciarelli J, Aswad S, Jabbour N, Selby R. Expanding the donor kidney pool: utility of renal allografts procured in a setting of uncontrolled cardiac death. Am J Transplant. 2006 Jul;6(7):1682-8. doi: 10.1111/j.1600-6143.2006.01386.x.

  PMID: 16827871 BACKGROUND

• Foroutan F, Friesen EL, Clark KE, Motaghi S, Zyla R, Lee Y, Kamran R, Ali E, De Snoo M, Orchanian-Cheff A, Ribic C, Treleaven DJ, Guyatt G, Meade MO. Risk Factors for 1-Year Graft Loss After Kidney Transplantation: Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol. 2019 Nov 7;14(11):1642-1650. doi: 10.2215/CJN.05560519. Epub 2019 Sep 20.

  PMID: 31540931 BACKGROUND

• de Sandes-Freitas TV, Felipe CR, Aguiar WF, Cristelli MP, Tedesco-Silva H, Medina-Pestana JO. Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals. PLoS One. 2015 Dec 17;10(12):e0144188. doi: 10.1371/journal.pone.0144188. eCollection 2015.

  PMID: 26679933 BACKGROUND

• Dawidson IJ, Sandor ZF, Coorpender L, Palmer B, Peters P, Lu C, Sagalowsky A, Risser R, Willms C. Intraoperative albumin administration affects the outcome of cadaver renal transplantation. Transplantation. 1992 Apr;53(4):774-82. doi: 10.1097/00007890-199204000-00014.

  PMID: 1566343 BACKGROUND

• Willms CD, Dawidson IJ, Dickerman R, Drake D, Sandor ZF, Trevino G. Intraoperative blood volume expansion induces primary function after renal transplantation: a study of 96 paired cadaver kidneys. Transplant Proc. 1991 Feb;23(1 Pt 2):1338-9. No abstract available.

  PMID: 1989234 BACKGROUND

• Lewis SR, Pritchard MW, Evans DJ, Butler AR, Alderson P, Smith AF, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018 Aug 3;8(8):CD000567. doi: 10.1002/14651858.CD000567.pub7.

  PMID: 30073665 BACKGROUND

• Weimar W, Geerlings W, Bijnen AB, Obertop H, van Urk H, Lameijer LD, Wolff ED, Jeekel J. A controlled study on the effect of mannitol on immediate renal function after cadaver donor kidney transplantation. Transplantation. 1983 Jan;35(1):99-101. No abstract available.

  PMID: 6401883 BACKGROUND

• Tiggeler RG, Berden JH, Hoitsma AJ, Koene RA. Prevention of acute tubular necrosis in cadaveric kidney transplantation by the combined use of mannitol and moderate hydration. Ann Surg. 1985 Feb;201(2):246-51. doi: 10.1097/00000658-198502000-00020.

  PMID: 3918517 BACKGROUND

• von Moos S, Akalin E, Mas V, Mueller TF. Assessment of Organ Quality in Kidney Transplantation by Molecular Analysis and Why It May Not Have Been Achieved, Yet. Front Immunol. 2020 May 12;11:833. doi: 10.3389/fimmu.2020.00833. eCollection 2020.

  PMID: 32477343 BACKGROUND

• Reiterer C, Hu K, Sljivic S, Falkner von Sonnenburg M, Fleischmann E, Kainz A, Kabon B. Mannitol and renal graft injury in patients undergoing deceased donor renal transplantation - a randomized controlled clinical trial. BMC Nephrol. 2020 Jul 28;21(1):307. doi: 10.1186/s12882-020-01961-z.

  PMID: 32723374 BACKGROUND

• Gremmels H, de Jong OG, Toorop RJ, Michielsen L, van Zuilen AD, Vlassov AV, Verhaar MC, van Balkom BWM. The Small RNA Repertoire of Small Extracellular Vesicles Isolated From Donor Kidney Preservation Fluid Provides a Source for Biomarker Discovery for Organ Quality and Posttransplantation Graft Function. Transplant Direct. 2019 Aug 12;5(9):e484. doi: 10.1097/TXD.0000000000000929. eCollection 2019 Sep.

  PMID: 31579812 BACKGROUND

• Siew ED, Ware LB, Ikizler TA. Biological markers of acute kidney injury. J Am Soc Nephrol. 2011 May;22(5):810-20. doi: 10.1681/ASN.2010080796. Epub 2011 Apr 14.

  PMID: 21493774 BACKGROUND

• Tataruch-Weinert D, Musante L, Kretz O, Holthofer H. Urinary extracellular vesicles for RNA extraction: optimization of a protocol devoid of prokaryote contamination. J Extracell Vesicles. 2016 Jun 24;5:30281. doi: 10.3402/jev.v5.30281. eCollection 2016.

  PMID: 27345058 BACKGROUND

• Feng Y, Lv LL, Wu WJ, Li ZL, Chen J, Ni HF, Zhou LT, Tang TT, Wang FM, Wang B, Chen PS, Crowley SD, Liu BC. Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy. Am J Pathol. 2018 Nov;188(11):2542-2552. doi: 10.1016/j.ajpath.2018.07.017. Epub 2018 Aug 22.

  PMID: 30142333 BACKGROUND

MeSH Terms

Interventions

Mannitol; Sodium Chloride

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Evitar Neser

CONTACT

972528488884; eviatarne@clalit.org.il

Atara Davis

CONTACT

atarada@clalit.org.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2021
• First Posted: January 12, 2021
• Study Start: February 1, 2022
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: January 22, 2021

Record last verified: 2021-01