Hypotension and Shock, Intraoperative Hypotension, Kidney Transplant; Complications, Postoperative Hypotension, Shock, Shock, Surgical
Conditions
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.
Interventions
DRUGAngiotensin 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.
Sponsors
La Jolla Pharmaceutical Company
University of Illinois at Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of ATII Vasopressor Usage in the Intraoperative Setting | Duration of usage during the transplant surgery - presented in hours | Duration of vasopressor usage while in the operating room measured in hours of usage presented as median and IQR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | The presence of digital or other peripheral/visceral ischemia was captured from reviewing chart documentation for each patient. |
| 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. | Incidence of venous or arterial thrombosis occurring during the hospitalization for kidney transplant (captured by ultrasound or other diagnostic imaging) |
| 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. | The presence of arrhythmia was confirmed via EKG, flowsheet, or note documentation from the electronic medical record. |
| 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. | 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. |
| Number (and Percentage) of Patients With Delayed Graft Function | From post-op to 7 days post-op | 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. |
| 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. | The presence of post-operative fungal infections were captured prior to discharge as documented by the clinical care team in the electronic medical record. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Angiotensin II (Giapreza) The study group received angiotensin II (Giapreza) as the first continuous infusion vasopressor as clinically indicated for either intraoperative or postoperative hypotension not responsive to fluids or push dose vasopressors (intraoperative only). | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Angiotensin II (Giapreza) |
|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized Black | 7 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 6 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
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.
Time frame: Duration of usage during the transplant surgery - presented in hours
Population: Started ATII intraoperatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Angiotensin II (Giapreza) | Duration of ATII Vasopressor Usage in the Intraoperative Setting | 1 hours |
Secondary
Number (and Percentage) of Patients With Arrhythmias
The presence of arrhythmia was confirmed via EKG, flowsheet, or note documentation from the electronic medical record.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Angiotensin II (Giapreza) | Number (and Percentage) of Patients With Arrhythmias | 1 Participants |
Secondary
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.
Time frame: From post-op to 7 days post-op
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Angiotensin II (Giapreza) | Number (and Percentage) of Patients With Delayed Graft Function | 2 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Angiotensin II (Giapreza) | Number (and Percentage) of Patients With Fungal Infections | 0 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Angiotensin II (Giapreza) | Number (and Percentage) of Patients With Hyperglycemia | 1 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Angiotensin II (Giapreza) | Number (and Percentage) of Patients With Peripheral/Visceral Ischemia | 0 Participants |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Angiotensin II (Giapreza) | Number (and Percentage) of Patients With Thrombosis | 0 Participants |