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

NCT04529005 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 2020-0526
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Shock, Surgical; Shock; Hypotension and Shock; Kidney Transplant; Complications; Intraoperative Hypotension; Postoperative Hypotension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number (and Percentage) of Patients With Arrhythmias

  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

  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

  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

  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

  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.

Study Arms (1)

Angiotensin II (Giapreza)

EXPERIMENTAL

Drug: Angiotensin II

Interventions

Angiotensin II DRUG

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.

Angiotensin II (Giapreza)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• La Jolla Pharmaceutical Company: collaborator

Study Sites (1)

University of Illinois Hospital and Health Sciences System

Chicago, Illinois, 60612, United States

Location

Related Publications (12)

• 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.

  PMID: 25948896 BACKGROUND

• 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.

  PMID: 31514910 BACKGROUND

• 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.

  PMID: 22841277 BACKGROUND

• 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.

  PMID: 24768292 BACKGROUND

• 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.

  PMID: 28072739 BACKGROUND

• 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.

  PMID: 20005360 BACKGROUND

• 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.

  PMID: 28528561 BACKGROUND

• 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.

  PMID: 29077618 BACKGROUND

• 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.

  PMID: 20381298 BACKGROUND

• 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.

  PMID: 9850443 BACKGROUND

• 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.

  PMID: 29509568 BACKGROUND

• 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.

  PMID: 23835589 BACKGROUND

MeSH Terms

Conditions

Shock, Surgical; Shock; Hypotension

Interventions

Angiotensin II

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors

Results Point of Contact

• Title: Scott Benken
• Organization: University of Illinois Chicago College of Pharmacy

benken@uic.edu

3123554107

Study Officials

• Scott T Benken, PharmD

  Clinical Associate Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 27, 2020
• Study Start: August 13, 2020
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: December 21, 2022
• Results First Posted: December 21, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)