Angiotensin II in the Perioperative Management of Hypotension in Kidney Transplant Recipients

Angiotensin II in the Perioperative Management of Hypotension in Kidney Transplant

The current standard of catecholamine vasopressor management of perioperative hypotension in kidney transplant patients carries significant risks and falls short in many ways. Currently, there is an absence in the scientific literature and research describing the hemodynamic effectiveness and safety of novel pharmacologic agents such as angiotensin II (Giapreza - Ang II) in perioperative kidney transplant patients. Phase 3 registration trials have demonstrated the superior safety and efficacy of Ang II (Giapreza) in distributive shock patients compared to traditional vasopressor agents and the novel mechanism of action may provide additional protection in renal transplant patients. The pilot study entails giving informed and consenting kidney transplant recipients Ang II (Giapreza) as their first vasopressor if the need for vasopressors emerge either intraoperatively or postoperatively in kidney transplant recipients. The primary objective is to evaluate the safety and hemodynamic effects of Ang II (Giapreza) in the renal transplant population.

Study Overview

• Status: Completed
• Conditions: Shock; Kidney Transplant; Complications; Hypotension and Shock; Intraoperative Hypotension; Shock, Surgical; Postoperative Hypotension
• Intervention / Treatment: Drug: Angiotensin II

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital and Health Sciences System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients > 18 years of age
• Receiving deceased donor kidney transplant
• Pre-transplant Ejection Fraction (within past 18 months) > 50%
• Intraoperative or postoperative distributive shock (according to hospital and study protocol) requiring vasopressor support

Exclusion Criteria:

• Pregnant patients (they would be excluded from receiving a transplant)
• Prisoners
• History of mesenteric ischemia
• History of aortic dissection
• History of abdominal aortic aneurysm
• Allergy to mannitol
• Absolute neutrophil count < 1000 cell/mm3 (within past 18 months)
• Diagnosis of Raynaud's phenomenon, systemic sclerosis or vasospastic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Angiotensin II (Giapreza)	Drug: Angiotensin II; If intraoperative or postoperative hypotension occurs (e.g. SBP < 120 mmHg) and the attending surgeon and/or attending anesthesiologist deems vasopressor therapy to be necessary, angiotensin II (Giapreza) will be the first vasopressor used for management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of ATII Vasopressor Usage in the Intraoperative Setting	Duration of vasopressor usage while in the operating room measured in hours of usage presented as median and IQR.	Duration of usage during the transplant surgery - presented in hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number (and Percentage) of Patients With Arrhythmias	The presence of arrhythmia was confirmed via EKG, flowsheet, or note documentation from the electronic medical record.	From date and time of study drug initiation during or after transplant operation until study drug is discontinued up to a maximum of 30 days.
Number (and Percentage) of Patients With Peripheral/Visceral Ischemia	The presence of digital or other peripheral/visceral ischemia was captured from reviewing chart documentation for each patient.	From date and time of study drug initiation during or after transplant operation until study drug is discontinued up to a maximum of 30 days.
Number (and Percentage) of Patients With Thrombosis	Incidence of venous or arterial thrombosis occurring during the hospitalization for kidney transplant (captured by ultrasound or other diagnostic imaging)	From date and time of study drug initiation during or after transplant operation until study drug is discontinued up to a maximum of 30 days.
Number (and Percentage) of Patients With Fungal Infections	The presence of post-operative fungal infections were captured prior to discharge as documented by the clinical care team in the electronic medical record.	From date and time of study drug initiation during or after transplant operation until study drug is discontinued up to a maximum of 30 days.
Number (and Percentage) of Patients With Hyperglycemia	The presence of hyperglycemia was captured for each patient and was determined by those patients requiring the use of an insulin infusion after their transplant surgery.	From date and time of study drug initiation during or after transplant operation until study drug is discontinued up to a maximum of 30 days.
Number (and Percentage) of Patients With Delayed Graft Function	The presence of Delayed Graft Function was captured for each patient and defined by the need for renal replacement therapy up to 7 days post-operative.	From post-op to 7 days post-op

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: La Jolla Pharmaceutical Company
• Investigators: Principal Investigator: Scott T Benken, PharmD, Clinical Associate Professor

Publications and helpful links

General Publications

• Aulakh NK, Garg K, Bose A, Aulakh BS, Chahal HS, Aulakh GS. Influence of hemodynamics and intra-operative hydration on biochemical outcome of renal transplant recipients. J Anaesthesiol Clin Pharmacol. 2015 Apr-Jun;31(2):174-9. doi: 10.4103/0970-9185.155144.
• Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.
• Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.
• Busse LW, Ostermann M. Vasopressor Therapy and Blood Pressure Management in the Setting of Acute Kidney Injury. Semin Nephrol. 2019 Sep;39(5):462-472. doi: 10.1016/j.semnephrol.2019.06.006.
• Campos L, Parada B, Furriel F, Castelo D, Moreira P, Mota A. Do intraoperative hemodynamic factors of the recipient influence renal graft function? Transplant Proc. 2012 Jul-Aug;44(6):1800-3. doi: 10.1016/j.transproceed.2012.05.042.
• Day KM, Beckman RM, Machan JT, Morrissey PE. Efficacy and safety of phenylephrine in the management of low systolic blood pressure after renal transplantation. J Am Coll Surg. 2014 Jun;218(6):1207-13. doi: 10.1016/j.jamcollsurg.2014.01.058. Epub 2014 Mar 12.
• Choi JM, Jo JY, Baik JW, Kim S, Kim CS, Jeong SM. Risk factors and outcomes associated with a higher use of inotropes in kidney transplant recipients. Medicine (Baltimore). 2017 Jan;96(1):e5820. doi: 10.1097/MD.0000000000005820.
• Ciapetti M, di Valvasone S, di Filippo A, Cecchi A, Bonizzoli M, Peris A. Low-dose dopamine in kidney transplantation. Transplant Proc. 2009 Dec;41(10):4165-8. doi: 10.1016/j.transproceed.2009.08.058.
• Lankadeva YR, Kosaka J, Evans RG, Bellomo R, May CN. Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation During Angiotensin II Therapy in Septic Acute Kidney Injury. Crit Care Med. 2018 Jan;46(1):e41-e48. doi: 10.1097/CCM.0000000000002797.
• Robert R, Guilhot J, Pinsard M, Longeard PL, Jacob JP, Gissot V, Hauet T, Seguin F. A pair analysis of the delayed graft function in kidney recipient: the critical role of the donor. J Crit Care. 2010 Dec;25(4):582-90. doi: 10.1016/j.jcrc.2010.02.011. Epub 2010 Apr 8.
• Toth M, Reti V, Gondos T. Effect of recipients' peri-operative parameters on the outcome of kidney transplantation. Clin Transplant. 1998 Dec;12(6):511-7.
• Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, Kashani K, Szerlip HM, Prowle JR, Bihorac A, Finkel KW, Zarbock A, Forni LG, Lynch SJ, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Bellomo R; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med. 2018 Jun;46(6):949-957. doi: 10.1097/CCM.0000000000003092. Erratum In: Crit Care Med. 2018 Aug;46(8):e824.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: November 26, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Shock; Hypotension; Shock, Surgical; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Vasoconstrictor Agents; Angiotensin II; Giapreza; Angiotensinogen
• Other Study ID Numbers: 2020-0526 (Other Identifier: M D Anderson Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes