Systemic Inflammatory Response Syndrome, C.Surgical Procedure; Cardiac
Conditions
Keywords
Inflammation, Systemic Inflammatory Response Syndrome, Pathologic Processes, Organ Dysfunction
Brief summary
The trial enrolls patients undergoing a complex cardiac surgery. The primary goal of the trial is to evaluate the pharmacodynamic dose response relationship of the monoclonal antibody IFX-1 in these patients. In addition, this trial further aims to characterize the safety and the pharmacokinetics of IFX-1 as well as to collect first data on its efficacy on clinical surrogate endpoints.
Interventions
BIOLOGICALIFX-1
BIOLOGICALPlacebo
Sponsors
InflaRx GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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): * Single valve surgery in combination with at least two coronary artery bypass grafts (CABGs) * Multiple valve surgery with or without CABG * Single or multiple valve surgery in combination with ascending aorta procedure with or without additional CABG * Re-surgery of aortic valve, mitral valve, aortic arch or ascending aorta with or without CABG 4. Cardiac surgery is performed electively
Exclusion criteria
1. Weight \> 130 kg 2. The following cardiac surgical procedures: * Cardiac surgical procedure is planned as minimally invasive procedure (e.g., without thoracotomy or with lateral incision, minimal thoracotomy) * Cardiac surgery with an expected CPB time less than 100 minutes 3. Other cardiac and vascular diseases and/or procedures: * Prior cardiac surgery within the past 6 months * History of heart transplantation or planned heart transplantation * Requiring inotropic, vasopressor or mechanical circulatory support * Requiring ventilatory support 4. Other disease or condition that is likely to interfere with the evaluation of the study drug: * Active infective endocarditis * Stroke or transient ischemic attack (TIA) within the last 6 months * Concomitant disease with a life expectancy of less than 6 months * Cardiopulmonary resuscitation within the last 4 weeks * 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: * Fever \> 38.0°C or hypothermia \< 36.0°C * Tachycardia \> 90 beats/minute * Tachypnea \> 20 breaths/minute * 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: * Hemoglobin \< 5 mmol/l (\< 8.06 g/dl) * Total bilirubin ≥ 2 x upper normal limit (UNL) * CRP \> 3 x UNL * ALAT \> 3 x UNL * ASAT \> 3 x UNL * White blood cell count \< 2,500/mm³ * White blood cell count \> 12,000/mm³ 10. Prohibited concomitant medications: * Immunomodulatory drugs within past 30 days (e.g., TNF-inhibitors) * Immunosuppressive drugs within past 30 days (e.g., cyclosporine, tacrolimus) * High dose corticosteroids (e.g., \> 50 mg prednisone/day or equivalent) within past 14 days * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak level of IL-6 | From prior study drug administration until 24h after start of cardiopulmonary bypass (CPB) (CPB) |
Secondary
| Measure | Time frame |
|---|---|
| Maximum observed concentration (Cmax) of IFX-1 | Data will be collected at the following approximate time points: prior study drug administration; 30 min after start of infusion; up to 10 min after cessation of CPB; 3h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15 |
| Area under the curve (AUC) of plasma concentration of IFX-1 | Data will be collected at the following approximate time points: prior study drug administration; 30 min after start of infusion; up to 10 min after cessation of CPB; 3h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15 |
| Plasma concentration of free, detectable C5a at each timepoint measured | Data will be collected at the following approximate time points: prior study drug administration, prior start of CPB, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15 |
| Serum levels of CH50 at each timepoint measured | Data will be collected at the following approximate time points: prior study drug administration, prior start of CPB, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15 |
| Serum levels of IL-6 compared to baseline | Data will be collected at the following approximate time points: prior study drug administration, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, and 96h after start of CPB; Day 15 |
| Serum levels of IL-8 compared to baseline | Data will be collected at the following approximate time points: prior study drug administration, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, and 96h after start of CPB; Day 15 |
| Plasma concentration of IFX-1 at each timepoint measured | Data will be collected at the following approximate time points: prior study drug administration; 30 min after start of infusion; up to 10 min after cessation of CPB; 3h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15 |
| Number of patients with detection of anti-drug-antibodies | Up to Day 15 |
| Number of patients that are successfully extubated 24h after end of surgery | 24h after end of surgery |
| Number of patients with consecutive invasive ventilation for more than 48h after end of surgery | 48h after end of surgery |
| Number of patients that are weaned of any vasopressor use 24h after end of surgery | 24h after end of surgery |
| Number of patients with SIRS 24h, 48h and 96h after start of CPB | 24h, 48h and 96h after start of CPB |
| Incidence of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) until Day 29 | From screening visit until Day 29 |
Countries
Germany
Outcome results
None listed