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Studying Complement Inhibition in Complex Cardiac Surgery (CARDIAC)

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ClinicalTrials.gov Identifier: NCT02866825
Recruitment Status : Completed
First Posted : August 15, 2016
Last Update Posted : February 15, 2017
Sponsor:
Information provided by (Responsible Party):
InflaRx GmbH

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.

Condition or disease Intervention/treatment Phase
Systemic Inflammatory Response Syndrome C.Surgical Procedure; Cardiac Biological: IFX-1 Biological: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2016
Actual Primary Completion Date : December 2016
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
Active Comparator: IFX-1
dose escalating single i.v. administration of IFX-1 (verum)
Biological: IFX-1
Placebo Comparator: Placebo
dose escalating mimicing single i.v. administration of placebo
Biological: Placebo



Primary Outcome Measures :
  1. Peak level of IL-6 [ Time Frame: From prior study drug administration until 24h after start of cardiopulmonary bypass (CPB) (CPB) ]

Secondary Outcome Measures :
  1. Plasma concentration of IFX-1 at each timepoint measured [ Time Frame: 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 ]
  2. Maximum observed concentration (Cmax) of IFX-1 [ Time Frame: 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 ]
  3. Area under the curve (AUC) of plasma concentration of IFX-1 [ Time Frame: 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 ]
  4. Plasma concentration of free, detectable C5a at each timepoint measured [ Time Frame: 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 ]
  5. Serum levels of CH50 at each timepoint measured [ Time Frame: 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 ]
  6. Serum levels of IL-6 compared to baseline [ Time Frame: 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 ]
  7. Serum levels of IL-8 compared to baseline [ Time Frame: 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 ]
  8. Incidence of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) until Day 29 [ Time Frame: From screening visit until Day 29 ]
  9. Number of patients with detection of anti-drug-antibodies [ Time Frame: Up to Day 15 ]
  10. Number of patients that are successfully extubated 24h after end of surgery [ Time Frame: 24h after end of surgery ]
  11. Number of patients with consecutive invasive ventilation for more than 48h after end of surgery [ Time Frame: 48h after end of surgery ]
  12. Number of patients that are weaned of any vasopressor use 24h after end of surgery [ Time Frame: 24h after end of surgery ]
  13. Number of patients with SIRS 24h, 48h and 96h after start of CPB [ Time Frame: 24h, 48h and 96h after start of CPB ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 exclusion criteria:

    • Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women
    • 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
    • Participation in any interventional clinical trial within the last three months
    • Prior randomization in this clinical trial (screen failures can be re-screened, if appropriate)
    • Alcohol, drug, or medication abuse
    • 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
    • No commitment to full aggressive life support (e.g., DNR order)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866825


Locations
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Germany
Study Site
Aachen, Germany
Study Site
Dortmund, Germany
Study Site
Dresden, Germany
Study Site
Freiburg, Germany
Study Site
Heidelberg, Germany
Study Site
Jena, Germany
Study Site
Kiel, Germany
Study Site
Leipzig, Germany
Study Site
Trier, Germany
Study Site
Tuebingen, Germany
Sponsors and Collaborators
InflaRx GmbH
Investigators
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Principal Investigator: Torsten Doenst, Prof. Dr. University Hospital Jena

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Responsible Party: InflaRx GmbH
ClinicalTrials.gov Identifier: NCT02866825     History of Changes
Other Study ID Numbers: IFX-1-P2.2
2015-003036-12 ( EudraCT Number )
First Posted: August 15, 2016    Key Record Dates
Last Update Posted: February 15, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by InflaRx GmbH:
Inflammation
Systemic Inflammatory Response Syndrome
Pathologic Processes
Organ Dysfunction

Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock