Reduction of Allogenic Blood Transfusion in Locally Advanced Kidney Cancer

Study Overview
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Brief Summary
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The Reduction of Allogenic Blood Transfusion in Locally Advanced Kidney Cancer Trial (RESTRICT). The primary objective is to reduce the number of units of allogenic blood transfusion in locally advanced kidney cancer (≥ cT2). Secondary objectives include reduction in perioperative complications, assessment of recurrence free-survival and improving overall survival.

Detailed Description
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The Reduction of Allogenic Blood Transfusion in Locally Advanced Kidney Cancer Trial (RESTRICT) is a randomized study to investigate blood sparing using autologous normovolemic hemodilution (ANH) or cell salvage at the time of nephrectomy for locally advanced kidney cancer after assessing inclusion criteria patients will be randomized to undergo standard blood management including the possibility of allogenic transfusion vs autologous blood transfusion. There are multiple ways patients can receive allogenic or autologous blood, including veno-venous bypass or cardiopulmonary bypass (typically reserved for patients with a thrombus above the level of the hepatic veins or entering the heart).

Official Title
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Reduction of Allogenic Blood Transfusion in Locally Advanced Kidney Cancer

Conditions
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Kidney Cancer

Intervention / Treatment
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* Procedure: Blood Sparing Protocol
* Procedure: Standard Blood Replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal masses ≥ cT2 (by any conventional imaging). N1 or M1 disease is allowed if they are deemed surgical candidates (including cytoreductive nephrectomy). Male and female patients. 18 and older. Ejection fraction (EF) ≥ 45% by echocardiogram (ECHO). Adequate organ function as defined by: Hemoglobin ≥ 9 g/dL. Pre-operative allogenic blood transfusion is allowed. Platelets ≥ 100.000/μl. Albumin ≥ 2.5 g/dL. Aspartate Aminotransferase (AST) and alanine transaminase (ALT) ≤ 75U/L or total bilirubin ≤ 2.0 mg/dL. WBC within institutional normal limits. PT within institutional normal limits. INR < 1.5 and PTT normal. Consent and compliance with all aspects of the study protocol. Exclusion Criteria: Male and female younger than 18 years old. Non-surgical candidate Unstable angina.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood Sparing Protocol<br>The intervention group (120 patients) will undergo radical nephrectomy with blood-sparing techniques. Acute Normovolemic Hemodilution (ANH) collects patients own blood prior to the start of surgical procedure; Cell saver is the collection of blood lost during surgery with subsequent auto-transfusion of the patients own cells; Veno-venous bypass will be used for patients with anticipated large loss of blood during surgery (>1L). The patients in the interventional group will be blinded to which blood sparing techniques utilized. | Procedure: Blood Sparing Protocol<br>* Acute Normovolemic Hemodilution, Cell Saver, and/or Veno-venous Bypass<br>|
| Active Comparator: Standard Blood Replacement<br>The control group of one hundred and twenty (120) patients will undergo radical nephrectomy without blood sparing techniques (ie. Standard of care). Patients who need blood transfusion will receive cross-matched allogenic blood products. | Procedure: Standard Blood Replacement<br>* Allogenic blood transfusion as determined intra-operatively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of units of allogenic blood transfusions | The primary goal of the study is to evaluate the impact of the blood sparing techniques on the reduction of allogenic blood transfusion in locally advanced kidney cancer. The total number of allogenic blood units used at the end of each case will be assessed | Baseline to 30 days postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Complications | Number of complications will be assessed by Clavien-Dindo Index Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions Grade II Pharmacological treatment with drugs other than such allowed for grade I. Grade III Requiring surgical, endoscopic or radiological intervention IIIa Not under general anesthesia IIIb Under general anesthesia Grade IV Life-threatening complication (including CNS complications)* requiring IC/ICU- management IVa single organ dysfunction (including dialysis) IVb multiorgan dysfunction Grade V Death | Baseline to 30 days and 90 days postoperatively | 
| Grade of Complications | Grade of complications will be assessed by Clavien-Dindo Index Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions Grade II Pharmacological treatment with drugs other than such allowed for grade I. Grade III Requiring surgical, endoscopic or radiological intervention IIIa Not under general anesthesia IIIb Under general anesthesia Grade IV Life-threatening complication (including CNS complications)* requiring IC/ICU- management IVa single organ dysfunction (including dialysis) IVb multiorgan dysfunction Grade V Death | Baseline to 30 days and 90 days postoperatively | 
| Kidney Cancer Recurrence | Assessment of recurrence of kidney cancer by radiographic imaging (CT or MRI) | Up to 3 years postoperatively | 
| Overall Survival | Assessment of survival after surgery | Up to 3 years postoperatively | 
| Quality of life as measured by Functional Assessment of Cancer Therapy-Kidney Symptom Index (FSKI-19) | Assessment of quality of life measures postoperatively, scores range from 0-76, with higher scores indicating worse symptoms Score range: 0-76 A score of 0 is a severely symptomatic patient and the highest possible score is an asymptomatic patient. | Pre-operative, 1 and 3 months postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nephrectomy, blood sparing, allogenic blood transfusion