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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Preventive Medicine, Multi Organ Failure

Intervention / Treatment
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* Drug: Interferon Beta-1A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FP-1201-lyo 10 µg<br>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. | Drug: Interferon Beta-1A<br>* Lyophilisate for solution for injection.<br>* Other names: ATC code L03AB07;|
| Placebo Comparator: FP-1201-lyo Placebo<br>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 | Drug: Placebo<br>* Lyophilisate for solution for injection as placebo.<br>* Other names: Placebo for investigational drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | Number of fatalities | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | Number of fatalities | Day 90 | 
| 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. | Day 30 | 
| 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. | Day 30 and Day 90 | 
| 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. | Day 30 | 
| 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. | Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay | 
| 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. | 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. | Day 90 | 
| 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. | Day 0 to Day 30 | 
| 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 | Day 30 or Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patients Surviving Open Surgery, Ruptured Abdominal Aortic Aneurysm