Acute Kidney Injury Urological and Genital Diseases Acute Kidney Injury
Conditions
Interventions
Participants are randomly allocated into a control group and an experimental group. Sildenafil or glucose (placebo) will be given intravenously as a bolus dose then infusion. Sildenafil 10mg (made up
Sponsors
University of Leicester (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current: 1. Adult cardiac surgery patients (>18 years) undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. 2. Identified as representing a high risk group for AKI using a modified AKI risk score; a predicted risk score of 22% equates to a positive predicted value for developing AKI of >55%. 3. Female subjects of childbearing potential are not to be pregnant (to be confirmed by urine human chorionic gonadotropin pregnancy test prior to dosing). Women are considered not to be of childbearing potential if they have been surgically sterilised (eg, tubal ligation, oophorectomy or hysterectomy) or are postmenopausal in the absence of hormone replacement therapy and complete absence of menses for at least 24 consecutive months. 4. Able, in the opinion of the investigator, and willing to give informed consent. Previous: 1. Adult cardiac surgery patients (>18 years) undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. 2. Identified as representing a high risk group for AKI using a modified AKI risk score; a predicted risk score of 22% equates to a positive predicted value for developing AKI of >55%.
Exclusion criteria
Exclusion criteria: Current: 1. Emergency or salvage procedure 2. Ejection fraction <20% 3. CKD Stage 5, defined as eGFR<15ml/min (as per the Modified diet in Renal Disease formula ) or renal replacement therapy. 4. Patients with a pre-existing sepsis or organ injury defined as documented sepsis, acute kidney injury, acute lung injury, myocardial infarction, low cardiac output, liver injury, stroke or pancreatitis within 5 days of surgery. 5. Administration of potent CYP 3A4 inhibitors within 1 month prior to study participation (e.g. HIV protease inhibitors, imidazole antifungals and erythromycin, 6. Administration of nitrate medicines (e.g. glyceryl trinitrate) within 24 hours of surgery. 7. Patients allergic to any other PDE-5 Inhibitor. 8. Patients who are participating in another interventional clinical study. 9. Patients who have loss of vision in one eye due to non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether it is connected to previous PDE5 inhibitor exposure. 10. Any ongoing malignancy or prior malignancy that currently requires treatment. 11. Female subjects of childbearing potential are not to be pregnant. 12. Cardiac surgery patients (<18 years) undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. 13. Severe hepatic impairment. 14. Severe hypotension (blood pressure < 90/50 mmHg) on the day prior to surgery. 15. Administration of the guanylate cyclase stimulators, such as riociguat. 16. Unable, in the opinion of the investigator, or unwilling to give informed consent. Previous: 1. Emergency or salvage procedure 2. Ejection fraction <20% 3. CKD Stage 5, defined as eGFR<15ml/min (as per the Modified diet in Renal Disease formula ) or renal replacement therapy. 4. Patients with a pre-existing sepsis or organ injury defined as documented sepsis, acute kidney injury, acute lung injury, myocardial infarction, low cardiac output, liver injury, stroke or pancreatitis within 5 days of surgery. 5. Administration of potent CYP 3A4 inhibitors within 1 month prior to study participation (e.g. HIV protease inhibitors, imidazole antifungals and erythromycin, 6. Administration of nitrate medicines (e.g. glyceryl trinitrate) within 24 hours of surgery. 7. Patients allergic to any other PDE-5 Inhibitor. 8. Patients who are participating in another interventional clinical study. 9. Patients who have loss of vision in one eye due to non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether it is connected to previous PDE5 inhibitor exposure. 10. Any ongoing malignancy or prior malignancy that currently requires treatment. 11. Female subjects of childbearing potential are not to be pregnant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum creatinine measured from daily blood tests for up to 7 days post-surgery or discharge if earlier. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current: 1. Acute Kidney Injury (AKI) Defined according to the KDIGO criteria defined as a rise in serum creatinine of >26µmol.l-1 within 48 hours or a doubling of the serum creatinine within 7 days of surgery. Serum creatinine measured at baseline, return from theatre, 6-12 hours post op, 24, 48, 72, 96, day 5, day 6 (or discharge), day 7 (or discharge) and 6 weeks 2. Changes in biochemical markers of renal injury and dysfunction (urine neutrophil gelatinase-associated lipocalin (NGAL)), and myocardial injury (serum troponin), measured at baseline, 6-12 hours post-op, and 48 hours post-op 3. Acute lung injury, low cardiac output, acute brain injury, acute liver or gut injury, sepsis syndrome, death. As per MOD Score including patient follow ups at ICU admission, 24, 48, 72 and 96 hours, day 5, day 6 (or discharge), day 7 (or discharge) and 6 weeks 4. Multiple Organ Dysfunction (MOD) Score at Pre op, ICU admission, 24, 48, 72 and 96 hours. 5. Length of ICU and hospital stay. Patient follow ups 6. Vital sign measurements and vasopressor use during and after drug administration. 7. Postoperative blood loss, transfusion of RBC and non RBC allogenic blood components. Patient follow ups post op 8. Expected adverse events other than those included in the primary endpoint. Patient follow ups 9. Endothelial function as measured by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index. Baseline and 24 hours by ENDO-PAT 10. Laboratory measures of platelet, leucocyte and endothelial cell activation from blood samples pre op, 6-12 hours & 48 hours Previous: 1. Acute Kidney Injury (AKI) Defined according to the KDIGO criteria defined as a rise in serum creatinine of >26µmol.l-1 within 48 hours or a doubling of the serum creatinine within 7 days of surgery. Serum creatinine m | — |
Countries
England, United Kingdom
Contacts
Public ContactTracy Kumar
Outcome results
None listed