Dexmedetomidine and Kidney Transplantation

NCT05935293 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: Dex Renal Transp
• Study Type: interventional
• Target: 206
• Locations: 0 countries
• Sites: N/A

Brief Summary

Dexmedetomidine, an alpha 2 agonist, is being increasingly used in recent years for the maintaining of anesthesia as it allows sedation and analgesia with only a modest respiratory depression effect when compared to opioids and inhaled anesthetic agents and allows maintenance of spontaneous ventilation. Most common side effects are bradycardia and hypotension. Drug's metabolism is exclusively hepatic and therefor do not require dosage adaptation for patient's kidney function. Post-Operative acute kidney injury (AKI) is a common complication after major surgery and might incur serious adverse outcomes such as longer hospital stay, dialysis, chronic kidney disease and death. The most common theory for the occurrence of post-operative AKI is the ischemic-reperfusion syndrome. Several in vitro animal studies as well as human studies have suggested the nephroprotective effects of per-operative continuous infusion of dexmedetomidine and its ability to decrease post-operative AKI. Kidney transplantation (KT) is the treatment of choice for patients with End Stage Renal Disease. It is considered a major surgery and it was shown that optimized perioperative management could improve post-operative outcomes such as early graft function as measured by urine output and serum creatinine trends. However, delayed graft function (DGF), which is defined by the need for dialysis within the first seven days after transplantation remains a significant issue for post-operative KT care with an incidence of up to 30%. A retrospective study of 780 patients receiving KT, has shown that preoperative dexmedetomidine could significantly decrease occurrence of DGF. Recently, two single-center, randomized controlled trials, with similar sample sizes of 104 and 111 patients, compared peri-operative continuous infusion of dexmedetomidine to placebo. One study failed to show significant impact on DGF incidence while the second showed a significant 50% reduction in DGF in the dexmedetomidine group. Due to increasing evidence concerning the nephroprotective effects and improved post-operative outcomes of perioperative continuous dexmedetomidine infusion, a larger, multi-center randomized-controlled trial to study and potentially confirm the evidence in the settings of KT would be of benefit. The aim of our study is to assess whether the perioperative continuous infusion of dexmedetomidine during KT could improve peri-operative renal function among KT recipients as compared to placebo.

Conditions

Renal Transplantation; Dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• Kinetic GFR

  The main outcome of the study is a significant increase in GFR kinetic values on postoperative day 1 (POD1) between the intervention and control groups after continuous perioperative infusion of dexmedetomidine.

  30-days

Secondary Outcomes (8)

• Impact of dexmedetomidine on delayed graft function assessing kGFR

  1-year

• Impact of dexmedetomidine on delayed graft function assessing GFR EPI

  1-year

• Impact of dexmedetomidine on delayed graft function monitoring serum creatinine levels

  1-year

• Impact of dexmedetomidine on delayed graft function evaluating urine output

  1-year

• Impact of dexmedetomidine on renal glomerular biomarkers

  3-days

Study Arms (2)

Dexmedetomidine

EXPERIMENTAL

Patients in the dexmedetomidine group will receive intraoperative dexmedetomidine initiated in the operating room, before anesthetic induction. Bolus of 0.6/mcg/Kg 15 mins before induction, followed by a continuous infusion of 0.4 mcg/kg/h during the per-operative period until transfer to intensive care and then 0.1 mcg/kg/h continued for additional 24 hours.

Drug: Dexmedetomidine

Control

PLACEBO COMPARATOR

Patients in the control group will receive intraoperative sodium chloride 0.9% initiated in the operating room, before anesthetic induction. IV administration rate will be weight adapted and similar to that of Dexmedetomidine group in volume (mL) and time (minutes) Bolus of 0.6/mcg/Kg 15 mins before induction, followed by a continuous infusion of 0.4 mcg/kg/h during the per-operative period until transfer to intensive care and then 0.1 mcg/kg/h continued for additional 24 hours.

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

iv administration dexmedetomidine

Also known as: DEX

Control; Dexmedetomidine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Elective and urgent renal transplantation for end-stage renal insufficiency

You may not qualify if:

• Age \< 18 years old
• Any known allergy or hypersensitivity to dexmedetomidine or clonidine
• Preoperative bradycardia with heart rate \<50
• Second or third-degree atrioventricular block
• Left ventricular ejection fraction \<30%
• Preoperative severe systolic dysfunction (LVEF\<30%)
• Conduction disorders of the Mobitz 2 or Mobitz 3 type in the absence of a pacemaker
• Exposure to Dexmedetomidine in the past 30 days
• Recent cerebrovascular pathology (\< 3 month)

Sponsors & Collaborators

• Eduardo Schiffer: lead

MeSH Terms

Interventions

Dexmedetomidine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: July 7, 2023
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 8, 2024

Record last verified: 2023-07