A Study to Determine the Pharmacokinetic Profile, Safety and Tolerability of Sildenafil (REVATIO®) in Cardiac Surgery

NCT02136329 | Completed Phase 1 DMC

• 1 other identifier: 0359
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration versus time curve and Plasma Concentration of Sildenafil

  There will be Pharmacokinetic sample collection pre and post dose to look at plasma concentration of sildenafil. Sample collection timepoints are post dose at 10 mins, 15 mins, 30 mns, 45 mins 2 hours, 4 hours, 12 hours, 24 hours and 48 hours.

  48 Hours

Secondary Outcomes (1)

• Serum creatinine and Biochemical markers of AKI

  5 Days

Other Outcomes (1)

• Adverse Events

  6 Weeks

Study Arms (1)

Sildenafil

EXPERIMENTAL

All subjects in groups 1-6 will receive SIldenafil but in escalating doses.

Drug: Sildenafil

Interventions

Sildenafil DRUG

The active study drug, Revatio®, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE5). Sildenafil citrate is designated chemically as 1-\[\[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo \[4,3-d\] pyrimidin-5-yl)-4-ethoxyphenyl\] sulfonyl\]-4-methylpiperazine citrate. The active study medication is supplied in single use glass vials and as a clear, colourless, sterile, ready-to-use solution containing 10 mg (12.5 mL) of sildenafil. Each mL of solution contains 1.124 mg sildenafil citrate, 50.5 mg dextrose and water for injection. Sildenafil is manufactured under Good Manufacturing Practice (EU-GMP) by Pfizer Inc

Also known as: REVATIO®

Sildenafil

Eligibility Criteria

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

You may qualify if:

• Adult cardiac surgery patients (\>18 years) undergoing cardiac surgery with moderately hypothermic CPB (32-34°C) and blood cardioplegia
• Identified as representing a high risk group for acute kidney injury using a modified risk score based on the variables of Age, Sex, BMI, Smoking Status, NHYA class, Previous Operations, Peripheral Vascular Disease, Diabetes, Hypertension, Pre-operative Haemoglobin level, Pre-operative eGFR, Operative Priority, Operation Type, Ejection Fraction and Presence of Pre-Operative Critical Events.
• 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 (defined as serum follicle-stimulating hormone level of ≥30 IU/mL) in the absence of hormone replacement therapy and complete absence of menses for at least 24 consecutive months.

You may not qualify if:

• Emergency or salvage procedure
• Ejection fraction \<30%
• CKD Stage 5, defined as eGFR\<15ml/min or renal replacement therapy.
• Administration of potent CYP 3A4 inhibitors within 1 month prior to study participation (e.g. HIV protease inhibitors, imidazole antifungals and erythromycin, please see Appendix 1 for a full list of prohibited medications).
• Administration of nitrate medicines (e.g. glyceryl trinitrate within 24 hours of surgery.
• Any ongoing malignancy, or prior malignancy that currently requires treatment.
• Patients allergic to any other PDE-5 Inhibitor
• Patients who are participating in another interventional clinical study

Sponsors & Collaborators

• University of Leicester: lead
• British Heart Foundation: collaborator

Study Sites (1)

Department of Cardiovascular Sciences.

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gavin Murphy, Prof

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 13, 2014
• Study Start: June 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 30, 2020

Record last verified: 2014-12

Locations

GB (1)