Clinical trial NCT02126332: Epidural Analgesia for Pancreatitis (Epipan Study)
Official title: A MULTICENTER, RANDOMIZED, CONTROLLED STUDY OF EPIDURAL ANALGESIA FOR SEVERE ACUTE PANCREATITIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Acute Pancreatitis
Keywords: Severe acute pancreatitis
Epidural analgesia
Acute respiratory failure
Mechanical ventilation
Intensive Care Unit (ICU)
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2014-04-30
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute pancreatitis (AP) is a common disease whose incidence in the US reaches 35 per 100,000 population annually. Its main causes in adults are gallstone migration into the common bile duct and alcohol abuse. Approximately 80% of patients with AP will develop a mild disease for which the management is mainly conservative. However 20% will develop a severe form, which is known to be associated with the development of local complications, such as pancreatic and peripancreatic necrosis, pseudocysts, and systemic complications, such as adult respiratory distress syndrome or renal failure. In the severe form of AP the mortality rate can reach 17% mainly due to multiple organ failure and pancreatic necrosis. In particular, pancreatic necrosis is associated with a death rate of up to 40%.

Epidural anesthesia (EA) is widely used to induce analgesia in the perioperative period and has also been used to decrease pain in patients with AP. In addition, experimental studies have shown a specific beneficial effect of EA in AP, attributed to an anti-inflammatory effect of local anesthetics administered in the epidural space combined with a sympathetic nerve blockade, which redistributes splanchnic blood flow to non-perfused pancreatic regions.

To date, EA has not been adequately tested in intensive care unit (ICU) patients with severe AP, with regards to clinical outcome. The objective of our study is therefore to test the effect of EA on lung dysfunction during severe AP, as we hypothesize that EA could limit lung failure requiring invasive mechanical ventilation (MV) or the duration of invasive MV

Detailed description: BACKGROUND:

Mild acute pancreatitis has a low mortality rate, but patients with severe acute pancreatitis (AP) are more likely to have complications and a much higher death rate. Severe pancreatic injury occurs in 20% of the patients, and 15% to 25% of these patients will not survive. The amplifying effects of inflammatory and oxidative impairment often lead to SAP-induced complications, which are often regarded as hallmarks of severe AP and herald a noted poor outcome. Since respiratory failure is the main cause of death in patients with severe AP, more work is needed for us to prevent and treat AP-associated lung dysfunction Despite recent substantial improvements in the multidisciplinary management of AP (with special emphasis on fluid therapy, intensive care management, prevention of infectious complications, nutritional support, biliary tract management or necrotizing pancreatitis management), the prognosis of severe AP remains poor in patients who develop acute respiratory failure requiring intubation and invasive respiratory support.

Animal studies suggest that epidural analgesia (EA) may decrease the severity of AP. EA is associated with sympathetic nerve blockade, which redistributes splanchnic blood flow to non-perfused pancreatic regions, and it may improve the pancreatic hypoperfusion induced by AP. EA also decreases the severity of metabolic acidosis and tissue injury, thus preventing the progression from an edematous disease to a necrotizing AP.

To date, EA has not been adequately tested in patients with severe AP as compared to conventional management, and with special emphasis on its putative beneficial ventilatory effects.

DESIGN NARRATIVE:

The purpose of this multicenter, prospective, randomized, controlled, trial is to test the effects of thoracic EA on pulmonary outcome in patients with severe AP.

After inclusion, ICU patients with severe AP will be randomized into 2 groups: a " conventional group " in which available guidelines on analgesia are applied, and an " EA " group in which patients receive thoracic EA for at least 3 days. Beyond the analgesic strategy, recent consensual guidelines on the management of severe AP are applied.

Eligibility criteria: Inclusion Criteria:

* Patients admitted to the ICU for acute pancreatitis

Exclusion Criteria:

* Absolute contra-indication for thoracic epidural catheter placement (Prothrombin time \< 60%, Platelet count \< 75G/l, curative anticoagulant therapy interrupted for less than 8 hours, local infection, active central nervous system infection, history of back surgery associated with a dural space procedure, suspected or confirmed intracranial hypertension, refractory circulatory shock)
* Refractory circulatory shock despite appropriate resuscitation
* Known allergy to ropivacain, sufentanil or clonidine
* Age under 18

Primary outcomes:
measure: Ventilator-free days
timeFrame: at day 30
Secondary outcomes:
measure: Duration of invasive and/or non invasive mechanical ventilation
timeFrame: at day 30
measure: incidence of various complications
timeFrame: at day 30
measure: Biological inflammatory response
timeFrame: at inclusion (day 0), on day 2 and day 7
measure: Cost analysis of severe AP management
timeFrame: at day 30
measure: Incidence of the intolerance to enteral feeding
timeFrame: from inclusion to day 30
measure: Effectiveness of pain management
timeFrame: from day 0 to day 30
measure: Duration of EA (Epidural anesthesia) therapy
timeFrame: from day 0 to day 30 after inclusion
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Matthieu JABAUDON
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bulyez S, Pereira B, Caumon E, Imhoff E, Roszyk L, Bernard L, Buhler L, Heidegger C, Jaber S, Lefrant JY, Chabanne R, Bertrand PM, Laterre PF, Guerci P, Danin PE, Escudier E, Sossou A, Morand D, Sapin V, Constantin JM, Jabaudon M; EPIPAN Study Group; AzuRea network. Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol. BMJ Open. 2017 May 29;7(5):e015280. doi: 10.1136/bmjopen-2016-015280.