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Epidural Analgesia for Pancreatitis (Epipan Study) (EPIPAN)

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ClinicalTrials.gov Identifier: NCT02126332
Recruitment Status : Unknown
Verified May 2014 by University Hospital, Clermont-Ferrand.
Recruitment status was:  Recruiting
First Posted : April 30, 2014
Last Update Posted : May 28, 2014
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

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


Condition or disease Intervention/treatment Phase
Severe Acute Pancreatitis Other: ropivacaine and sufentanil Other: acetaminophen, nefopam, tramadol, opidoids Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A MULTICENTER, RANDOMIZED, CONTROLLED STUDY OF EPIDURAL ANALGESIA FOR SEVERE ACUTE PANCREATITIS
Study Start Date : April 2014
Estimated Primary Completion Date : April 2017
Estimated Study Completion Date : April 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Conventional group
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.
Other: acetaminophen, nefopam, tramadol, opidoids
Conventional analgesia will include enteral and/or parental administration of usual analgesics, ranging from step 1 to step 3 drugs according to WHO classification (including acetaminophen, nefopam, tramadol, opidoids). The route, dose and frequency of analgesics administrations will be based on participating ICUs protocols.

Experimental: EA group (Epidural anesthesia )
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.
Other: ropivacaine and sufentanil
Thoracic epidural analgesia will be performed using ropivacaine (2 mg/ml), sufentanil (0.5 microg/ml) administered through a patient-controlled deviced (PCEA : patient-controlled epidural analgesia). PCEA parameters will be fixed as follows : continuous administration of 5 to 15 ml/h and bolus of 3 to 10 ml every 10 minutes. Iterative epidural administration of clonidine (1 mckg/kg) will be allowed to achieve analgesia goals.




Primary Outcome Measures :
  1. Ventilator-free days [ Time Frame: at day 30 ]
    (defined as the number of days from day 1 to day 30 on which a patient is able to breathe without invasive assistance. A difference in ventilator-free days can reflect a difference in mortality, ventilator days among survivors, or both.)


Secondary Outcome Measures :
  1. Duration of invasive and/or non invasive mechanical ventilation [ Time Frame: at day 30 ]
  2. incidence of various complications [ Time Frame: at day 30 ]
    (death, organ failure, severe sepsis, septic shock, acute respiratory distress syndrome (ARDS), acute respiratory failure, abdominal compartment syndrome, intra- or extra-abdominal infections, pancreatic necrosis or abscess (infected or not), hemodynamic failure requiring vasopressor therapy, acute renal failure, requirement for renal replacement therapy, infected intra-abdominal abscesses requiring drainage (radiological, endoscopic or surgical).

  3. Biological inflammatory response [ Time Frame: at inclusion (day 0), on day 2 and day 7 ]
    (biomarker analyses) : plasma levels of interleukin-6, soluble RAGE (receptor for advanced glycation end-products) and neutrophil gelatinase-associated lipocalin (NGAL), urine levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein7 (IGFBP-7) (Nephrocheck, Astute Medical)

  4. Cost analysis of severe AP management [ Time Frame: at day 30 ]
  5. Incidence of the intolerance to enteral feeding [ Time Frame: from inclusion to day 30 ]
  6. Effectiveness of pain management [ Time Frame: from day 0 to day 30 ]
    (pain assessment scores : visual analogic scale, behavioral pain scale)

  7. Duration of EA (Epidural anesthesia) therapy [ Time Frame: from day 0 to day 30 after inclusion ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02126332


Contacts
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Contact: Patrick LACARIN 04 73 75 11 95 placarin@chu-clermontferrand.fr

Locations
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France
CHU de Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63003
Contact: Patrick LACARIN    04 73 75 11 95    placarin@chu-clermontferrand.fr   
Sub-Investigator: Jean-Michel CONSTANTIN         
Sub-Investigator: Léo BUHLER         
Sub-Investigator: Jean-Yves LEFRANT         
Sub-Investigator: Bernard CLAUD         
Sub-Investigator: Russell CHABANNE         
Sub-Investigator: Pierre-Marie BERTRAND         
Sub-Investigator: Pierre-François LATERRE         
Sub-Investigator: Arnaud FRIGGERI         
Sub-Investigator: Samir JABER         
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
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Principal Investigator: Matthieu JABAUDON University Hospital, Clermont-Ferrand

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT02126332     History of Changes
Other Study ID Numbers: CHU-0188
2013-004652-37
First Posted: April 30, 2014    Key Record Dates
Last Update Posted: May 28, 2014
Last Verified: May 2014

Keywords provided by University Hospital, Clermont-Ferrand:
Severe acute pancreatitis
Epidural analgesia
Acute respiratory failure
Mechanical ventilation
Intensive Care Unit (ICU)

Additional relevant MeSH terms:
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Pancreatitis
Pancreatic Diseases
Digestive System Diseases
Ropivacaine
Sufentanil
Tramadol
Acetaminophen
Nefopam
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Antipyretics
Analgesics, Opioid
Narcotics
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General