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Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA (INFORAAA)

Primary Purpose

Preventive Medicine, Multi Organ Failure

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Interferon Beta-1A
Placebo
Sponsored by
Faron Pharmaceuticals Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Preventive Medicine focused on measuring Patients Surviving Open Surgery, Ruptured Abdominal Aortic Aneurysm

Eligibility Criteria

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

Inclusion Criteria:

To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria during screening and prior to the first dose of study medication being administered on D0 (criteria 1 or 2 and all 3, 4 and 5):

  1. Patients (male or female) presenting with a ruptured abdominal aortic aneurysm (RAAA) diagnosed by ultrasound or CT-scan in the emergency room

    • all forms of infrarenal RAAAs with or without coexisting iliac aneurysms are included or

  2. Patients (male or female) presenting with symptoms of RAAA known to have an infrarenal AAA and proceeding straight to open repair without radiological assessment and confirmed rupture (=retroperitoneal haematoma) in operation

    and

  3. Aneurysma repair must be infra-renal, i.e. the proximal anastomosis must be below the renal arteries and the renal arteries have to stay intact. Temporary above the renal clamping can be used for a maximum of 30 minutes (total clamping time)

    and

  4. Patients providing informed consent

    and

  5. Age of 18 years or higher

Exclusion Criteria:

To be eligible for inclusion into this study, each patient must not meet any of the following exclusion criteria during screening or prior to the first dose of study medication being administered:

  1. Moribund patient not eligible for treatment in ICU or expected to survive surgery
  2. Markedly short life expectancy, e.g. advanced malignant disease
  3. Current participation in another experimental treatment protocol
  4. Significant congestive heart failure, defined as New York Heart Association (NYHA) class IV
  5. Current treatment with Interferon (IFN) alpha or IFN beta
  6. Dialysis therapy for chronic renal failure
  7. Irreversible shock from haemorrhage
  8. Unconsciousness or inability to give consent
  9. Ruptured Endovascular Aortic Repair (rEVAR) first (prior attempt for endovascular aortic repair for the current rupture)
  10. Diagnosed cirrhosis
  11. Pregnancy and women with child bearing potential without negative pregnancy test
  12. Rupture not confirmed by CT or intra-operatively (impending ruptures are excluded)

  13. RAAA requiring repair of the renal arteries or the proximal aorta

    • thoracoabdominal aneurysms requiring immediate repair
    • damaged renal arteries during emergency clamping requiring repair

Note:

  • temporary clamping above the renal arteries (max 30 min total clamping time above the renal arteries) does not lead to exclusion
  • ligation of the left renal vein does not lead to exclusion

Sites / Locations

  • Tartu University Hospital
  • Helsinki University Hospital
  • Central Finland Central Hospital
  • South Karelia Central Hospital
  • Oulu University Hospital
  • Tampere University Hospital
  • Turku University Hospital
  • Hospital of Lithuanian University of Health Sciences Kauno klinikos
  • Vilnius University Hospital Santaros klinikos

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FP-1201-lyo 10 µg

FP-1201-lyo Placebo

Arm Description

FP-12-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection.

FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection

Outcomes

Primary Outcome Measures

The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Number of fatalities

Secondary Outcome Measures

The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Number of fatalities
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
Number of days receiving hemodialysis. There were only few reported values other than zero.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score
Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero. Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference.
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days
Economic measurement: Length of ICU stay, in terms of ICU free days at D30 Length of hospital stay, in terms of hospital free days at D90 Length of stay at another health care facility at D90 The number of days on hemodialysis at D30 and at D90 The number of organ failure free days at D30 The number of ventilation free days at D30

Full Information

First Posted
March 3, 2017
Last Updated
December 22, 2020
Sponsor
Faron Pharmaceuticals Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT03119701
Brief Title
Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA
Acronym
INFORAAA
Official Title
A Randomised, Parallel Group 2:1 Comparison of the Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) and Placebo in the Prevention of Multi-Organ Failure on Patients Surviving Open Surgery for a Ruptured Abdominal Aortic Aneurysm
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Why Stopped
IDMC recommendation. Unexpectedly high use of concomitant corticosteroid treatment.
Study Start Date
February 18, 2017 (Actual)
Primary Completion Date
September 23, 2019 (Actual)
Study Completion Date
October 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Faron Pharmaceuticals Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A study to assess effectiveness and safety of a drug FP-1201-lyo (Recombinant Human Interferon Beta-1a) in the Prevention of Multi-Organ Failure on patients after Open Surgery for a Ruptured Abdominal Aortic Aneurysm
Detailed Description
This trial is multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm. Investigational medicinal product will be administered as post-surgical preventive treatment either 10µg FP-1201-lyo or placebo. Treatment will be administered daily every 24 hrs for 6 days. The first dose will be given after successful surgery at the point when the patient arrives to the Intensive Care Unit (ICU). Both treatment groups will receive standard supportive care. Aim is randomise and initiate treatment of 152 patients. For the final analysis, a minimum of 129 evaluable patients will be required.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preventive Medicine, Multi Organ Failure
Keywords
Patients Surviving Open Surgery, Ruptured Abdominal Aortic Aneurysm

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FP-1201-lyo 10 µg
Arm Type
Experimental
Arm Description
FP-12-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection.
Arm Title
FP-1201-lyo Placebo
Arm Type
Placebo Comparator
Arm Description
FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection
Intervention Type
Drug
Intervention Name(s)
Interferon Beta-1A
Other Intervention Name(s)
FP-1201-lyo, ATC code L03AB07
Intervention Description
Lyophilisate for solution for injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for investigational drug
Intervention Description
Lyophilisate for solution for injection as placebo.
Primary Outcome Measure Information:
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Description
Number of fatalities
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Description
Number of fatalities
Time Frame
Day 90
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
Description
Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero.
Time Frame
Day 30
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
Description
Number of days receiving hemodialysis. There were only few reported values other than zero.
Time Frame
Day 30 and Day 90
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score
Description
Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero. Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation.
Time Frame
Day 30
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
Description
Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.
Time Frame
Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
Description
IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30.
Time Frame
Day 30
Title
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
Description
Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference.
Time Frame
Day 90
Title
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
Description
Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.
Time Frame
Day 0 to Day 30
Title
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days
Description
Economic measurement: Length of ICU stay, in terms of ICU free days at D30 Length of hospital stay, in terms of hospital free days at D90 Length of stay at another health care facility at D90 The number of days on hemodialysis at D30 and at D90 The number of organ failure free days at D30 The number of ventilation free days at D30
Time Frame
Day 30 or Day 90
Other Pre-specified Outcome Measures:
Title
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker
Description
Concentration of Myxovirus Resistant Protein A (MxA)
Time Frame
Day 0 up to Day 13
Title
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples
Description
CD73 (ecto-5'-nucleotidase enzyme) concentration
Time Frame
Day 0 up to Day 13
Title
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples
Description
IL-6 concentration.
Time Frame
Day 0 up to Day 13
Title
Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples
Description
HGF concentration.
Time Frame
Day 0 up to Day 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria during screening and prior to the first dose of study medication being administered on D0 (criteria 1 or 2 and all 3, 4 and 5): Patients (male or female) presenting with a ruptured abdominal aortic aneurysm (RAAA) diagnosed by ultrasound or CT-scan in the emergency room all forms of infrarenal RAAAs with or without coexisting iliac aneurysms are included or Patients (male or female) presenting with symptoms of RAAA known to have an infrarenal AAA and proceeding straight to open repair without radiological assessment and confirmed rupture (=retroperitoneal haematoma) in operation and Aneurysma repair must be infra-renal, i.e. the proximal anastomosis must be below the renal arteries and the renal arteries have to stay intact. Temporary above the renal clamping can be used for a maximum of 30 minutes (total clamping time) and Patients providing informed consent and Age of 18 years or higher Exclusion Criteria: To be eligible for inclusion into this study, each patient must not meet any of the following exclusion criteria during screening or prior to the first dose of study medication being administered: Moribund patient not eligible for treatment in ICU or expected to survive surgery Markedly short life expectancy, e.g. advanced malignant disease Current participation in another experimental treatment protocol Significant congestive heart failure, defined as New York Heart Association (NYHA) class IV Current treatment with Interferon (IFN) alpha or IFN beta Dialysis therapy for chronic renal failure Irreversible shock from haemorrhage Unconsciousness or inability to give consent Ruptured Endovascular Aortic Repair (rEVAR) first (prior attempt for endovascular aortic repair for the current rupture) Diagnosed cirrhosis Pregnancy and women with child bearing potential without negative pregnancy test Rupture not confirmed by CT or intra-operatively (impending ruptures are excluded) RAAA requiring repair of the renal arteries or the proximal aorta thoracoabdominal aneurysms requiring immediate repair damaged renal arteries during emergency clamping requiring repair Note: temporary clamping above the renal arteries (max 30 min total clamping time above the renal arteries) does not lead to exclusion ligation of the left renal vein does not lead to exclusion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harri Hakovirta, MD
Organizational Affiliation
Turku University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Maarit Venermo, MD
Organizational Affiliation
Helsinki University Central Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tartu University Hospital
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Helsinki University Hospital
City
Helsinki
ZIP/Postal Code
FI-00290
Country
Finland
Facility Name
Central Finland Central Hospital
City
Jyväskylä
ZIP/Postal Code
FI-40620
Country
Finland
Facility Name
South Karelia Central Hospital
City
Lappeenranta
ZIP/Postal Code
FI-53130
Country
Finland
Facility Name
Oulu University Hospital
City
Oulu
ZIP/Postal Code
FI-90220
Country
Finland
Facility Name
Tampere University Hospital
City
Tampere
ZIP/Postal Code
FI-33520
Country
Finland
Facility Name
Turku University Hospital
City
Turku
ZIP/Postal Code
FFI-20520
Country
Finland
Facility Name
Hospital of Lithuanian University of Health Sciences Kauno klinikos
City
Kaunas
ZIP/Postal Code
LT-50161
Country
Lithuania
Facility Name
Vilnius University Hospital Santaros klinikos
City
Vilnius
ZIP/Postal Code
LT-08661
Country
Lithuania

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35115574
Citation
Hakovirta H, Jalkanen J, Saimanen E, Kukkonen T, Romsi P, Suominen V, Vikatmaa L, Valtonen M, Karvonen MK, Venermo M; INFORAAA Study Group. Induction of CD73 prevents death after emergency open aortic surgery for a ruptured abdominal aortic aneurysm: a randomized, double-blind, placebo-controlled study. Sci Rep. 2022 Feb 3;12(1):1839. doi: 10.1038/s41598-022-05771-1.
Results Reference
derived

Learn more about this trial

Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA

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