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Studying Complement Inhibition in Complex Cardiac Surgery (CARDIAC)

Primary Purpose

Systemic Inflammatory Response Syndrome, C.Surgical Procedure; Cardiac

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
IFX-1
Placebo
Sponsored by
InflaRx GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Inflammatory Response Syndrome focused on measuring Inflammation, Systemic Inflammatory Response Syndrome, Pathologic Processes, Organ Dysfunction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

IFX-1

Placebo

Arm Description

dose escalating single i.v. administration of IFX-1 (verum)

dose escalating mimicing single i.v. administration of placebo

Outcomes

Primary Outcome Measures

Peak level of IL-6

Secondary Outcome Measures

Plasma concentration of IFX-1 at each timepoint measured
Maximum observed concentration (Cmax) of IFX-1
Area under the curve (AUC) of plasma concentration of IFX-1
Plasma concentration of free, detectable C5a at each timepoint measured
Serum levels of CH50 at each timepoint measured
Serum levels of IL-6 compared to baseline
Serum levels of IL-8 compared to baseline
Incidence of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) until Day 29
Number of patients with detection of anti-drug-antibodies
Number of patients that are successfully extubated 24h after end of surgery
Number of patients with consecutive invasive ventilation for more than 48h after end of surgery
Number of patients that are weaned of any vasopressor use 24h after end of surgery
Number of patients with SIRS 24h, 48h and 96h after start of CPB

Full Information

First Posted
June 17, 2016
Last Updated
February 14, 2017
Sponsor
InflaRx GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT02866825
Brief Title
Studying Complement Inhibition in Complex Cardiac Surgery
Acronym
CARDIAC
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 Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
InflaRx GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Inflammatory Response Syndrome, C.Surgical Procedure; Cardiac
Keywords
Inflammation, Systemic Inflammatory Response Syndrome, Pathologic Processes, Organ Dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
116 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IFX-1
Arm Type
Active Comparator
Arm Description
dose escalating single i.v. administration of IFX-1 (verum)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
dose escalating mimicing single i.v. administration of placebo
Intervention Type
Biological
Intervention Name(s)
IFX-1
Intervention Type
Biological
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Peak level of IL-6
Time Frame
From prior study drug administration until 24h after start of cardiopulmonary bypass (CPB) (CPB)
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
Incidence of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) until Day 29
Time Frame
From screening visit until Day 29
Title
Number of patients with detection of anti-drug-antibodies
Time Frame
Up to Day 15
Title
Number of patients that are successfully extubated 24h after end of surgery
Time Frame
24h after end of surgery
Title
Number of patients with consecutive invasive ventilation for more than 48h after end of surgery
Time Frame
48h after end of surgery
Title
Number of patients that are weaned of any vasopressor use 24h after end of surgery
Time Frame
24h after end of surgery
Title
Number of patients with SIRS 24h, 48h and 96h after start of CPB
Time Frame
24h, 48h and 96h after start of CPB

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients ≥ 18 years old Written informed consent 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 Cardiac surgery is performed electively Exclusion Criteria: Weight > 130 kg 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 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 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 Cerebrovascular disease requiring concomitant carotid endarterectomy Active infection with or without a temperature greater than 38°C 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) Positive test for human immunodeficiency virus (HIV), hepatitis B or C 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 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 Planned corticosteroid pulse therapy to prevent SIRS Patients with known hypersensitivity to any constituent of the investigational medicinal product (IMP) 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Torsten Doenst, Prof. Dr.
Organizational Affiliation
University Hospital Jena
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study Site
City
Aachen
Country
Germany
Facility Name
Study Site
City
Dortmund
Country
Germany
Facility Name
Study Site
City
Dresden
Country
Germany
Facility Name
Study Site
City
Freiburg
Country
Germany
Facility Name
Study Site
City
Heidelberg
Country
Germany
Facility Name
Study Site
City
Jena
Country
Germany
Facility Name
Study Site
City
Kiel
Country
Germany
Facility Name
Study Site
City
Leipzig
Country
Germany
Facility Name
Study Site
City
Trier
Country
Germany
Facility Name
Study Site
City
Tuebingen
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

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Studying Complement Inhibition in Complex Cardiac Surgery

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