A phase II randomized, placebo-controlled, double-blind, dose-escalation study to evaluate safety, pharmacokinetics and pharmacodynamic dose response relationship of IFX-1 in patients undergoing complex cardiac surgery (CARDIAC)
- Conditions
- Prevention of organ dysfunction induced by inflammatory response after complex cardiac surgeryMedDRA version: 20.0Level: PTClassification code 10063101Term: Post procedural inflammationSystem Organ Class: 10022117 - Injury, poisoning and procedural complicationsMedDRA version: 20.0Level: LLTClassification code 10062357Term: SIRSSystem Organ Class: 100000004867Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]
- Registration Number
- EUCTR2015-003036-12-DE
- Lead Sponsor
- InflaRx GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- Not specified
1.Male or female patients = 18 years old
2.Written informed consent
3.One of the following cardiac surgical procedures is planned with Cardiopulmonary bypass (CPB):
a.Single valve surgery in combination with at least two coronary artery bypass grafts (CABGs)
b.Multiple valve surgery with or without CABG
c.Single or multiple valve surgery in combination with ascending aorta procedure with or without additional CABG
d.Re-surgery of aortic valve, mitral valve, aortic arch or ascending aorta with or without CABG
4.Cardiac surgery is performed electively
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
1.Weight > 130 kg
2.The following cardiac surgical procedures:
a.Cardiac surgical procedure is planned as minimally invasive procedure (e.g., without thoracotomy or with lateral incision, minimal thoracotomy)
b.Cardiac surgery with an expected CPB time less than 100 minutes
3.Other cardiac and vascular diseases and/or procedures:
a.Prior cardiac surgery within the past 6 months
b.History of heart transplantation or planned heart transplantation
c.Requiring inotropic, vasopressor or mechanical circulatory support
d.Requiring ventilatory support
4.Other disease or condition that is likely to interfere with the evaluation of the study drug:
a.Active infective endocarditis
b.Stroke or transient ischemic attack (TIA) within the last 6 months
c.Concomitant disease with a life expectancy of less than 6 months
d.Cardiopulmonary resuscitation within the last 4 weeks
e.Patients requiring renal replacement therapy
5.Cerebrovascular disease requiring concomitant carotid endarterectomy
6.Active infection with or without a temperature greater than 38°C
7.Presence of systemic inflammatory response syndrome defined as occurrence of at least 2 out of the following 4 criteria:
a.Fever > 38.0°C or hypothermia < 36.0°C
b.Tachycardia > 90 beats/minute
c.Tachypnea > 20 breaths/minute
d.Leucocytosis > 12 x 109/l or leucopenia < 4 x 109/l or > 10% immature neutrophils (bands)
8. Positive test for human immunodeficiency virus (HIV), hepatitis B or C
9.One of the following abnormal laboratory results:
a.Hemoglobin < 5 mmol/l (< 8.06 g/dl)
b.Total bilirubin = 2 x upper normal limit (UNL)
c.CRP > 3 x UNL
d.ALAT > 3 x UNL
e.ASAT > 3 x UNL
f.White blood cell count < 2,500/mm³
g.White blood cell count > 12,000/mm³
10.Prohibited concomitant medications:
a.Immunomodulatory drugs within past 30 days (e.g., TNF-inhibitors)
b.Immunosuppressive drugs within past 30 days (e.g., cyclosporine, tacrolimus)
c.High dose corticosteroids (e.g., > 50 mg prednisone/day or equivalent) within past 14 days
d.Any systemic anticancer treatment within the past 3 months
11.Planned corticosteroid pulse therapy to prevent SIRS
12. Patients with known hypersensitivity to any constituent of the
investigational medicinal product (IMP)
13.General exclusion criteria:
a.Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women
b.Women with childbearing potential (defined as within two years of their last menstruation) not willing to practice appropriate contraceptive measures (e.g., implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy, abstinence) while participating in the trial
c.Participation in any interventional clinical trial within the last three months
d.Prior randomization in this clinical trial (screen failures can be re-screened, if appropriate)
e.Alcohol, drug, or medication abuse
f.Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor
g.No commitment to full aggressive life support (e.g., DNR order)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of four different doses of IFX-1 on IL-6 peak levels in patients undergoing complex cardiac surgery compared to placebo.;Secondary Objective: To assess the pharmacokinetics and pharmacodynamics of IFX-1 and to characterize the safety and tolerability at different doses.<br><br>To evaluate a potential efficacy of IFX-1 on clinical surrogate endpoints (e.g., duration of mechanical ventilation, use of vasopressor, number of patients with Systemic inflammatory response syndrome (SIRS), Sequential organ failure assessment (SOFA) Score, length of intensive care unit (ICU) stay).<br>;Primary end point(s): The peak level of IL-6 in patients undergoing a complex cardiac surgery from prior to study drug administration until 24 hours after start of CPB.;Timepoint(s) of evaluation of this end point: From prior to study drug administration until 24 hours after start of CPB
- Secondary Outcome Measures
Name Time Method