Clinical trial NCT04529005: Angiotensin II in the Perioperative Management of Hypotension in Kidney Transplant Recipients
Official title: Angiotensin II in the Perioperative Management of Hypotension in Kidney Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Shock, Surgical
Shock
Hypotension and Shock
Kidney Transplant; Complications
Intraoperative Hypotension
Postoperative Hypotension
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: La Jolla Pharmaceutical Company
First posted: 2020-08-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Duration of ATII Vasopressor Usage in the Intraoperative Setting
timeFrame: Duration of usage during the transplant surgery - presented in hours
Secondary outcomes:
measure: Number (and Percentage) of Patients With Arrhythmias
timeFrame: 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.
measure: Number (and Percentage) of Patients With Peripheral/Visceral Ischemia
timeFrame: 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.
measure: Number (and Percentage) of Patients With Thrombosis
timeFrame: 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.
measure: Number (and Percentage) of Patients With Fungal Infections
timeFrame: 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.
measure: Number (and Percentage) of Patients With Hyperglycemia
timeFrame: 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.
measure: Number (and Percentage) of Patients With Delayed Graft Function
timeFrame: From post-op to 7 days post-op
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System
state: Illinois
Study officials:
affiliation: Clinical Associate Professor
name: Scott T Benken, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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