Severe Acute PancreatitisPhase 3EPIPANNCT02126332
Epidural Analgesia for Pancreatitis (Epipan Study)
A Phase 3 study testing ropivacaine and sufentanil and acetaminophen, nefopam, tramadol, opidoids in people with Severe Acute Pancreatitis, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Acute Pancreatitis
- What is being tested?
- ropivacaine and sufentanil and acetaminophen, nefopam, tramadol, opidoids
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteFrance
- Study dates
- 6 Jun 2014to 26 Feb 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients admitted to the ICU for acute pancreatitis
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A MULTICENTER, RANDOMIZED, CONTROLLED STUDY OF EPIDURAL ANALGESIA FOR SEVERE ACUTE PANCREATITIS
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
Read the 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.
- Conditions
- Severe Acute Pancreatitis
- Being tested
- ropivacaine and sufentanil, acetaminophen, nefopam, tramadol, opidoids
- Keywords
- Severe acute pancreatitis, Epidural analgesia, Acute respiratory failure, Mechanical ventilation, Intensive Care Unit (ICU)
- Medical subject headings
- Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ropivacaine and sufentanilOther
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.
acetaminophen, nefopam, tramadol, opidoidsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Conventional group | Other | 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. Receives: Other: acetaminophen, nefopam, tramadol, opidoids |
| EA group (Epidural anesthesia ) | Experimental | 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. Receives: Other: ropivacaine and sufentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventilator-free days
(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.)
Measured: at day 30
Secondary outcomes (7)
Duration of invasive and/or non invasive mechanical ventilation
Measured: at day 30
incidence of various complications
(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).
Measured: at day 30
Biological inflammatory response
(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)
Measured: at inclusion (day 0), on day 2 and day 7
Cost analysis of severe AP management
Measured: at day 30
Incidence of the intolerance to enteral feeding
Measured: from inclusion to day 30
Effectiveness of pain management
(pain assessment scores : visual analogic scale, behavioral pain scale)
Measured: from day 0 to day 30
Duration of EA (Epidural anesthesia) therapy
Measured: from day 0 to day 30 after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2014 (estimated)
- Study start6 Jun 2014
- Primary completion26 Feb 2019
- Study completion26 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Severe Acute PancreatitisStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthieu JABAUDON, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02126332
- Sponsor's protocol ID
- CHU-0188
- Other IDs
- 2013-004652-37
- Acronym
- EPIPAN
- Status last verified
- Jul 2026
- First submitted
- 11 Apr 2014
- Last updated
- 3 Aug 2026
- Results posted
- No
Publications
Jabaudon M, Genevrier A, Jaber S, Windisch O, Bulyez S, Laterre PF, Escudier E, Sossou A, Guerci P, Bertrand PM, Danin PE, Bonnassieux M, Buhler L, Heidegger CP, Chabanne R, Godet T, Roszyk L, Sapin V, Futier E, Pereira B, Constantin JM; EPIPAN study group. Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial. Crit Care. 2023 May 31;27(1):213. doi: 10.1186/s13054-023-04502-w.
PubMed 37259157Bulyez 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.
PubMed 28554928
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A MULTICENTER, RANDOMIZED, CONTROLLED STUDY OF EPIDURAL ANALGESIA FOR SEVERE ACUTE PANCREATITIS
- ClinicalTrials.gov ID
- NCT02126332
- Acronym / sponsor ID
- EPIPAN / CHU-0188
- Conditions
- Severe Acute Pancreatitis
- Keywords
- Severe acute pancreatitis, Epidural analgesia, Acute respiratory failure, Mechanical ventilation, Intensive Care Unit (ICU)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 6 Jun 2014 (actual)
- Primary completion
- 26 Feb 2019 (actual)
- Study completion
- 26 Feb 2019 (actual)
- First posted
- 30 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional group | Other | Other: acetaminophen, nefopam, tramadol, opidoids2 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. |
| EA group (Epidural anesthesia ) | Experimental | Other: ropivacaine and sufentanil2 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients admitted to the ICU for acute pancreatitis
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ropivacaine and sufentanilThoracic 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. | Other | EA group (Epidural anesthesia ) |
| acetaminophen, nefopam, tramadol, opidoidsConventional 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. | Other | Conventional group |
Primary outcome
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.)
7 secondary outcomes
Duration of invasive and/or non invasive mechanical ventilation
Time frame: at day 30
incidence of various complications
Time frame: at day 30
Biological inflammatory response
Time frame: at inclusion (day 0), on day 2 and day 7
Cost analysis of severe AP management
Time frame: at day 30
Incidence of the intolerance to enteral feeding
Time frame: from inclusion to day 30
Effectiveness of pain management
Time frame: from day 0 to day 30
Duration of EA (Epidural anesthesia) therapy
Time frame: from day 0 to day 30 after inclusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Results publication: PubMed 37259157Jabaudon M, Genevrier A, Jaber S, Windisch O, Bulyez S, Laterre PF, Escudier E, Sossou A, Guerci P, Bertrand PM, Danin PE, Bonnassieux M, Buhler L, Heidegger CP, Chabanne R, Godet T, Roszyk L, Sapin V, Futier E, Pereira B, Constantin JM; EPIPAN study group. Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial. Crit Care. 2023 May 31;27(1):213. doi: 10.1186/s13054-023-04502-w.
- Derived from this study: PubMed 28554928Bulyez 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthieu JABAUDON principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ropivacaine and sufentanil and acetaminophen, nefopam, tramadol, opidoids in people with Severe Acute Pancreatitis, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator-free days (time frame: at day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02126332, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.