Pharmacokinetic profile, safety and tolerability of Sildenafil (REVATIO®) in cardiac surgery patients with chronic kidney disease

A phase I study to determine the pharmacokinetic profile, safety and tolerability of Sildenafil (REVATIO®) in cardiac surgery patients with chronic kidney disease

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN37719011

Enrollment

Registered

2014-01-10

Start date

2013-04-01

Completion date

Unknown

Last updated

2016-11-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiac surgery patients with chronic kidney disease Urological and Genital Diseases Chronic kidney disease

Interventions

Patients will be screened by the investigators to assess eligibility for entry into the study. Eligible patients undergoing cardiac surgery with CPB who consent to participate will be consecutively al

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Adult cardiac surgery patients (>16 years and 15 and <90ml/min (International classification of Chronic Kidney Disease, CKD, Stage 2-4)

Exclusion criteria

Exclusion criteria: 1. Emergency or salvage procedure 2. Ejection fraction 90ml/min 4. CKD Stage 5, defined as eGFR<15ml/min or renal replacement therapy 5. Administration of potent CYP 3A4 inhibitors within 1 month prior to study participation 6. Any ongoing malignancy, or prior malignancy that currently requires treatment. 7. Patients allergic to any other PDE-5 Inhibitor 8. Patients who are participating in another interventional clinical study

Design outcomes

Primary

Measure	Time frame
1. Safety will be assessed by means of the following: 1.1. Physical examination at screening and clinical outcome monitoring during hospitalization and at 4-6 weeks follow-up visit 1.2. Vital sign measurements during study drug administration 1.3. Clinical laboratory assessments including haematology, biochemistry and urinalysis (at screening and at 6 hrs, 24 hrs, 48 hrs and 96 hrs after study drug administration and at hospital discharge) 1.4. Adverse events and concomitant medications/therapies 2. Pharmacokinetic assessments will include evaluation of plasma levels of Sildenafil and N-desmetyl-Sildenafil (at start of infusion, end of the bolus infusion and at 15 min, 30 min, 45 min, 1 hr, 2 hrs (end of CPB), 4 hrs (CICU admission), 6 hrs and 24 hrs after end of bolus infusion 3. Plasma levels of Sildenafil and the following pharmacokinetic parameters calculated from it: 3.1. Incremental recovery (peak recorded within the first hour after infusion) 3.2. Maximum plasma concentrations (Cmax) 3.3. Time to Cmax (Tmax) 3.4. Terminal half-life (t1/2) 3.5. Terminal elimination rate constant (kel) 3.6. Area under the plasma time versus concentration curve from time 0 to time of last measurable concentration (AUC(0-t)); linear trapezoidal method 3.7. Area under the plasma time versus concentration curve from time 0 to extrapolated to infinity (AUC(0-8)) 3.8. Clearance (CL) 3.9. Apparent volume of distribution (Vz) 3.10. Mean residence time (MRT)	—

Measure

Time frame

1. Safety will be assessed by means of the following: 1.1. Physical examination at screening and clinical outcome monitoring during hospitalization and at 4-6 weeks follow-up visit 1.2. Vital sign measurements during study drug administration 1.3. Clinical laboratory assessments including haematology, biochemistry and urinalysis (at screening and at 6 hrs, 24 hrs, 48 hrs and 96 hrs after study drug administration and at hospital discharge) 1.4. Adverse events and concomitant medications/therapies 2. Pharmacokinetic assessments will include evaluation of plasma levels of Sildenafil and N-desmetyl-Sildenafil (at start of infusion, end of the bolus infusion and at 15 min, 30 min, 45 min, 1 hr, 2 hrs (end of CPB), 4 hrs (CICU admission), 6 hrs and 24 hrs after end of bolus infusion 3. Plasma levels of Sildenafil and the following pharmacokinetic parameters calculated from it: 3.1. Incremental recovery (peak recorded within the first hour after infusion) 3.2. Maximum plasma concentrations (Cmax) 3.3. Time to Cmax (Tmax) 3.4. Terminal half-life (t1/2) 3.5. Terminal elimination rate constant (kel) 3.6. Area under the plasma time versus concentration curve from time 0 to time of last measurable concentration (AUC(0-t)); linear trapezoidal method 3.7. Area under the plasma time versus concentration curve from time 0 to extrapolated to infinity (AUC(0-8)) 3.8. Clearance (CL) 3.9. Apparent volume of distribution (Vz) 3.10. Mean residence time (MRT)

—

Secondary

Measure	Time frame
No secondary outcome measures	—

Countries

United Kingdom

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026