An Trial of Two Dosing Regimens of AP214 for the Prevention of Kidney Injury in Patients Undergoing Cardiac Surgery

An Explorative Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Trial of Two Dosing Regimens of AP214 for the Prevention of Kidney Injury in Patients Undergoing Cardiac Surgery

This study investigates the effect of two dose-levels of AP214 on the prevention of (acute) kidney injury after cardiac surgery.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Coronary Artery Bypass; Valve Surgery; Cardiac Surgery; Aortic Aneurysm
• Intervention / Treatment: Drug: AP214; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • University Hospital Copenhagen, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has signed the trial-specific informed consent form.
2. Patients ≥ 18 years old, male or female, not of childbearing potential (postmenopausal or permanently sterilized, e.g. tubal ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
3. Patients undergoing combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery), or
4. Patients undergoing surgery of more than one cardiac valve (valves surgery), or
5. Patients undergoing surgery of the aortic root or ascending part of the aorta, or
6. Patients undergoing surgery of the aortic root or ascending part of the aorta, combined with CABG and/or valve(s) surgery, or
7. Patients with stage III chronic kidney disease (eGFR 30-59 ml/min determined by the Modification of Diet in Renal Disease (MDRD formula)) undergoing CABG or Valve surgery

Exclusion Criteria:

1. Cardiac surgery to be performed "off pump" without cardiopulmonary bypass.
2. Cardiac surgery to be performed with hypothermic circulatory arrest.
3. Confirmed or suspected endocarditis.
4. EF ≤ 20%, evaluated within 2 months prior to screening visit.
5. Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure.
6. Active peptic ulcer disease and gastritis.
7. Receiving dopamine, adrenalin or noradrenalin at any dose at any time 14 days prior to Day of surgery.
8. Known or suspected hypersensitivity to the investigational medicinal product.
9. Current participation in any other interventional clinical trial.
10. Previously dosed with AP214.
11. Use of investigational medicinal products within the previous 6 months.
12. Body weight above 130 kg.
13. History of any organ transplant.
14. Women who are of childbearing potential, pregnant, or breast-feeding.
15. Current abuse of alcohol or substance, according to the investigator's medical judgment.
16. Has a mental incapacity or language barriers precluding adequate understanding of trial procedures.
17. Any history of cancer within the last 2 years
18. Any history of dialysis.
19. Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AP214; dose-level 1	Drug: AP214; AP214
EXPERIMENTAL: AP214; dose-level 2	Drug: AP214; AP214
PLACEBO_COMPARATOR: Placebo to AP214; Placebo	Drug: Placebo; Placebo; intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	To assess the safety and tolerability of AP214 compared to placebo; by analysis of number and nature of Adverse Events (AEs), Serious Adverse Events (SAEs), changes in laboratory parameters and overall health status	90 days
Efficacy	To assess the effect of AP214 versus placebo on the maximal postoperative change in absolute values of Serum Creatinine (SCr) compared to baseline within the first 7 days after surgery or until discharge from hospital, whichever comes first	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	To assess the ability of AP214 compared to placebo to reduce postoperative changes in SCr, and eGFR at day 28, 60 and Day 90 and GFR at Day 90 compared to baseline	90 days

Collaborators and Investigators

• Sponsor: Action Pharma A/S
• Investigators: Study Director: Action Pharma, Action Pharma A/S

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: December 5, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (ESTIMATE): December 8, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): March 15, 2012
• Last Update Submitted That Met QC Criteria: March 14, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Acute kidney injury; Cardiac surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Aortic Diseases; Kidney Diseases; Aneurysm; Aortic Aneurysm
• Other Study ID Numbers: AP214-CS007