Safety, Tolerability and Pharmacodynamics of AP214 Acetate in Patients Undergoing Cardiac Surgery

NCT00628264 | Terminated Phase 2 DMC

• 1 other identifier: AP214-CS004
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the present research study is to investigate for the first time, the safety and tolerability of infusion doses of AP214 in subjects having heart surgery such as coronary bypass graft and/or valve repair or replacement surgery. AP214, the investigational drug, is being developed to potentially prevent post-surgical kidney injury after thoracic aortic aneurysm repair.

Conditions

Cardiac Surgery; Coronary Artery Bypass Grafting; Valve Surgery; Kidney Injury

Keywords

cardiac surgery; coronary artery bypass grafting; valve surgery; acute kidney injury

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of AP214 administered as three 10-minute bolus infusions, in patients undergoing cardiac surgery that are at increased risk of AKI (descriptive analysis of AEs and SAEs from Day 0-14).

  From day 0-14

• To assess the impact of AP214 on cardiac surgery induced systemic inflammatory response syndrome determined by the post-operative peak plasma concentrations of IL-6 and IL-10 from 0-24 hours

  0-24 hours

Secondary Outcomes (4)

• To assess the safety and tolerability of AP214 at an organ level as well as in terms of the overall mortality (heart, CNS, lung, wound, mortality)

  Day 0-90

• To assess the impact of AP214 on cardiac surgery induced systemic inflammatory response syndrome (post-operative peak plasma concentrations of TNF-α and IL-8 and AUC for TNF-α, IL-6, IL-8 and IL-10).

  0-24 hours

• To assess the impact of AP214 for renal protection as measured by the development of post-surgical acute kidney injury (AKIN score)

  Day 0-14

• To assess the impact of AP214 on the development of post-surgical left ventricular dysfunction (determined by changes in left ventricular function from pre to post coronary bypass by transesophageal echocardiography

  0-24 hours

Study Arms (2)

AP214

EXPERIMENTAL

Drug: AP214

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AP214 DRUG

Three AP214 bolus infusions administered over 10 minutes (prior to skin incision, at time of clamp-release and 6 hours after clamp-release).

AP214

Placebo DRUG

Three placebo bolus infusions administered over 10 minutes (prior to skin incision, at time of clamp-release and 6 hours after clamp-release).

Placebo

Eligibility Criteria

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

You may qualify if:

• Has signed the trial specific informed consent form.
• Patients ≥ 18 years old, male or female, not of childbearing potential (postmenopausal or permanently sterilized e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
• Patients undergoing CABG, valve(s), CABG/valve and/or aortic root or ascending aortic aneurysm repair surgery.
• Cleveland Clinic Renal Score ≥ 2 (higher than average risk for AKI).
• EF ≥ 30%, evaluated within 2 months prior to screening visit.

You may not qualify if:

• Cardiac surgery to be performed "off pump" without cardiopulmonary bypass.
• Circulatory arrest in connection with aortic root or ascending aortic aneurysm repair surgery.
• Confirmed or suspected endocarditis.
• Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure.
• Receiving Aprotinin during the trial, from Screening to Day 90.
• Having undergone cardiovascular catheterization ≤ 48 hours prior to scheduled surgery.
• Active peptic ulcer disease and gastritis.
• Hemoccult positive stools, hematological, bleeding, and coagulation disorders.
• Receiving dopamine at renal doses (2-4 mcg/kg/min), from Screening to Day 90.
• S-Creatinine greater than 2.1 mg/dl.
• Known or suspected hypersensitivity to the investigational medicinal product.
• Known or suspected hypersensitivity to ondansetron or other selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.
• Current participation in any other interventional clinical trial.
• Previously dosed with AP214.
• Use of investigational medicinal products within the previous 6 months.

Sponsors & Collaborators

• Action Pharma A/S: lead

Study Sites (2)

Shands Hospital at Alachua General Hospital

Gainesville, Florida, 32601, United States

Location

Shands Hopsital at University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas M Beaver, MD, MPH

  Division of Thoracic and Cardiovascular Surgery , University of Florida College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 25, 2008
• First Posted: March 5, 2008
• Study Start: March 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: June 1, 2009

Record last verified: 2009-05

Locations

US (2)