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

Study Overview
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Brief Summary
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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.

Official Title
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Angiotensin II in the Perioperative Management of Hypotension in Kidney Transplant

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

Intervention / Treatment
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* Drug: Angiotensin II


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Angiotensin II (Giapreza)<br> | Drug: Angiotensin II<br>* 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.<br>|

What is the study measuring?
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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 |