Randomized, multicentre, double-blind, placebo-controlled trial of the use of aprotinin in the repair of ruptured abdominal aortic aneurysm

Abstract Background: Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). Methods: This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10μg) or matching placebo for 6 days after surgery. Major exclusion criteria included irreversible hemorrhagic shock, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 minutes. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. Results: The study was pre-maturely stopped due to a reported drug-drug interaction and was left under-powered. Out of 40 randomized patients 38 were included in the outcome analyses (27 IFN beta-1a and 11 placebo). There was no statistically significant difference between treatment groups at baseline. However, from surgery more open-abdomen and intestinal ischemia was present in the IFN beta-1a arm. D30 all-cause mortality was 22.2% (6/27) in the IFN beta-1a arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI, 0.21 – 8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the IFN beta-1a arm vs. 9.1% in the placebo arm). High level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids and the presence of IFN beta neutralizing antibodies associated with a poor CD73 response and survival.Conclusions: Due to the size of the study and several confounding factors a benefit from IFN beta-1a could not be determined. Survival after open RAAA surgery associated strongly with up-regulation of serum CD73. The use of glucocorticoids and IFN beta neutralizing antibodies blocked the up regulation of CD73. Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered).

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Induction of CD73 Prevents Death After Emergency Open Aortic Surgery for a Ruptured Abdominal Aortic Aneurysm – A Randomized, Double-Blind, Placebo-Controlled Study

10.21203/rs.3.rs-732466/v1 ◽

2021 ◽

Author(s):

Harri Hakovirta ◽

Juho Jalkanen ◽

Eija Saimanen ◽

Tiia Kukkonen ◽

Pekka Romsi ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Open Surgery ◽

Aortic Surgery ◽

Common Adverse Event ◽

Controlled Study ◽

Ruptured Abdominal Aortic Aneurysm ◽

Double Blind ◽

Abdominal Aortic ◽

All Cause Mortality

Abstract Background: Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). Methods: This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10μg) or matching placebo for 6 days after surgery. Major exclusion criteria included irreversible hemorrhagic shock, unconsciousness at arrival, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 minutes. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. Results: Out of 40 randomized patients 38 were included in the outcome analyses (27 active arm and 11 placebo). Treatment groups were comparable by baseline characteristics. D30 all-cause mortality was 22.2% (6/27) in the active arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI, 0.21 – 8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the active arm vs. 9.1% in the placebo arm). High level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids associated with a poor CD73 response and poor survival in the active arm (P = 0.002).Conclusions: IV IFN beta-1a was well tolerated. Survival after open RAAA surgery associated strongly with up-regulation of serum CD73, but the use of glucocorticoids blocked IFN beta-1a from up-regulating CD73. Trial registration: ClinicalTrials.gov NCT03119701Funding/Support: This study was sponsored by Faron Pharmaceuticals Ltd.

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01 / Efficacy of bilateral dual transversus abdominis plane (TAP) block for postoperative analgesia after open abdominal aortic aneurysm (AAA) surgery: a prospective monocentric randomized double-blind controlled trial

10.26226/morressier.5aeb0ac707b0d6001a79a293 ◽

2018 ◽

Author(s):

Elodie Dupont ◽

Elodie ['chenet']

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Postoperative Analgesia ◽

Controlled Trial ◽

Transversus Abdominis ◽

Tap Block ◽

Transversus Abdominis Plane ◽

Double Blind ◽

Abdominal Aortic

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Fenofibrate in the management of AbdoMinal aortic aneurysm (FAME)-2: the study protocol for a multi-centre, randomised, placebo-controlled trial

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20163960 ◽

2016 ◽

Vol 3 (4) ◽

pp. 217 ◽

Cited By ~ 3

Author(s):

Sophie E. Rowbotham ◽

Bernie Bourke ◽

Michael Bourke ◽

Rene Jaeggi ◽

Jason S. Jenkins ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Outcome Measures ◽

Medical Therapy ◽

Controlled Trial ◽

Aortic Aneurysms ◽

Secondary Outcome ◽

Controlled Clinical Trial ◽

Double Blind ◽

Abdominal Aortic

Background: Abdominal aortic aneurysms (AAAs) are a leading cause of mortality worldwide but have no recognised medical therapy. Pre-clinical studies indicate that osteopontin plays an important role in the pathogenesis of AAA via a number of mechanisms. This trial aims to assess the potential of fenofibrate to favourably alter biomarkers associated with AAA pathology. Methods: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME)-2 is a multi-centre, prospective, randomised, double-blind, placebo-controlled clinical trial to assess the effect of 24 weeks of oral therapy with 145 mg of fenofibrate on key pathological markers of AAA. A total of 140 participants with an AAA measuring between 35-49 mm will be randomly assigned to either 145 mg of fenofibrate once per day or identical placebo for a period of 24 weeks. Primary outcome measures will be serum concentrations of osteopontin and kallistatin. Secondary outcome measures will include serum levels of resistin, lipids, matrix metalloproteinases and pro-inflammatory cytokines, circulating concentrations of AAA biomarkers, and AAA diameter as assessed by ultrasound.Conclusions: This study represents the next step in the assessment of a potential novel medical therapy for AAA.

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Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion (Br J Surg 2001: 88: 1066-72)

British Journal of Surgery ◽

10.1046/j.0007-1323.2001.01998.x ◽

2002 ◽

Vol 89 (1) ◽

pp. 120-121

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Controlled Trial ◽

Double Blind ◽

Abdominal Aortic

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