Acute Kidney Injury Clinical Trial
Official title:
A Phase I Study to Determine the Pharmacokinetic Profile, Safety and Tolerability of Sildenafil (REVATIO®) in Cardiac Surgery
The objectives of the study are the following:
- To evaluate the pharmacokinetic profile of Sildenafil in cardiac surgery patients at
risk of acute kidney injury
- To determine the safety and tolerability of Sildenafil in cardiac surgery patients at
risk of acute kidney injury
Acute kidney injury occurs in up to one third of all patients following cardiac surgery. It
is manifested by an acute decline in kidney function and results in significant increases in
postoperative complications as well as an almost fourfold increase in the risk of
postoperative death. Our understanding of the underlying processes is poor and recent
systematic reviews have concluded that there is no effective treatment.
Experimental studies have demonstrated that preservation of endogenous Nitric Oxide (NO)
bioavailability is reno-protective in response to a variety of injurious stimuli. Endogenous
NO activity is increased by administration of the phosphodiesterase type 5 (PDE-5) inhibitor
sildenafil citrate. This is used clinically in the treatment of erectile dysfunction
(Viagra®, Pfizer) and more recently, pulmonary hypertension and acute right ventricular
failure (Revatio®, Pfizer). We have developed a preclinical swine model of extracorporeal
circulation (cardiopulmonary bypass) mediated acute kidney injury that shows significant
homology to that which occurs in post cardiac surgery patients. Administration of intravenous
sildenafil prevents acute kidney injury in this model in association with an increase in NO
bioavailability. There is a recognized clinical need for developing prevention and treatment
strategies for AKI and results obtained in this preclinical study indicate that Sildenafil is
suitable for further development as a potential prevention strategy for post cardiac surgery
AKI.
Prior to conducting a safety and efficacy trial however we intend to first establish a dose
of Sildenafil that is tolerated by cardiac surgery patients and compare the pharmacokinetics
of this dose to the effective dose identified in our preclinical work. We therefore propose
to evaluate the pharmacokinetic profile, safety and tolerability of sildenafil in 36 patients
undergoing cardiac surgery, in an open label, dose escalation Phase I study. This study will
inform the design of a subsequent randomized Phase IIb trial that will determine efficacy and
safety
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05538351 -
A Study to Support the Development of the Enhanced Fluid Assessment Tool for Patients With Acute Kidney Injury
|
||
| Recruiting |
NCT06027788 -
CTSN Embolic Protection Trial
|
N/A | |
| Completed |
NCT03938038 -
Guidance of Ultrasound in Intensive Care to Direct Euvolemia
|
N/A | |
| Recruiting |
NCT05805709 -
A Patient-centered Trial of a Process-of-care Intervention in Hospitalized AKI Patients: the COPE-AKI Trial
|
N/A | |
| Recruiting |
NCT05318196 -
Molecular Prediction of Development, Progression or Complications of Kidney, Immune or Transplantation-related Diseases
|
||
| Recruiting |
NCT05897840 -
Continuous Central Venous Oxygen Saturation Measurement as a Tool to Predict Hemodynamic Instability Related to Renal Replacement Therapy in Critically Ill Patients
|
N/A | |
| Recruiting |
NCT04986137 -
Fractional Excretion of Urea for the Differential Diagnosis of Acute Kidney Injury in Cirrhosis
|
||
| Terminated |
NCT04293744 -
Acute Kidney Injury After Cardiac Surgery
|
N/A | |
| Completed |
NCT04095143 -
Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury
|
||
| Not yet recruiting |
NCT06026592 -
Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients
|
||
| Not yet recruiting |
NCT06064305 -
Transcriptional and Proteomic Analysis of Acute Kidney Injury
|
||
| Terminated |
NCT03438877 -
Intensive Versus Regular Dosage For PD In AKI.
|
N/A | |
| Terminated |
NCT03305549 -
Recovery After Dialysis-Requiring Acute Kidney Injury
|
N/A | |
| Completed |
NCT05990660 -
Renal Assist Device (RAD) for Patients With Renal Insufficiency Undergoing Cardiac Surgery
|
N/A | |
| Completed |
NCT04062994 -
A Clinical Decision Support Trial to Reduce Intraoperative Hypotension
|
||
| Terminated |
NCT02860130 -
Clinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT)
|
Phase 3 | |
| Completed |
NCT06000098 -
Consol Time and Acute Kidney Injury in Robotic-assisted Prostatectomy
|
||
| Not yet recruiting |
NCT05548725 -
Relation Between Acute Kidney Injury and Mineral Bone Disease
|
||
| Completed |
NCT02665377 -
Prevention of Akute Kidney Injury, Hearttransplant, ANP
|
Phase 3 | |
| Terminated |
NCT03539861 -
Immunomodulatory Biomimetic Device to Treat Myocardial Stunning in End-stage Renal Disease Patients
|
N/A |