Clinical trial NCT03119701: Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Preventive Medicine
Multi Organ Failure
Keywords: Patients Surviving Open Surgery
Ruptured Abdominal Aortic Aneurysm
Lead sponsor: Faron Pharmaceuticals Ltd
Sponsor class: INDUSTRY
First posted: 2017-04-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

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.

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):

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

Primary outcomes:
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
timeFrame: Day 30
Secondary outcomes:
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
timeFrame: Day 90
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
timeFrame: Day 30
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
timeFrame: Day 30 and Day 90
measure: 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
timeFrame: Day 30
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
timeFrame: Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
timeFrame: Day 30
measure: The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
timeFrame: Day 90
measure: Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
timeFrame: Day 0 to Day 30
measure: 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
timeFrame: Day 30 or Day 90
Other outcomes:
measure: Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker
timeFrame: Day 0 up to Day 13
measure: Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples
timeFrame: Day 0 up to Day 13
measure: Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples
timeFrame: Day 0 up to Day 13
measure: Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples
timeFrame: Day 0 up to Day 13
Locations:
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Jyväskylä
country: Finland
facility: Central Finland Central Hospital
city: Lappeenranta
country: Finland
facility: South Karelia Central Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros klinikos
Study officials:
affiliation: Turku University Hospital
name: Harri Hakovirta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital
name: Maarit Venermo, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.