Trial of Aggressive Hydration Versus Rectal Indomethacin for Prevention of Post-ERCP Pancreatitis
Condition: Post-ERCP Acute Pancreatitis
MeSH terms: Pancreatitis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Endoscopic Retrograde Cholangiopancreatography (ERCP) is a commonly performed endoscopic
      procedure used to treat pancreato-biliary pathology. Acute pancreatitis or post-ERCP
      pancreatitis (PEP), is the most common major complication of ERCP, which is reported to occur
      in 2-10% of patients overall (ranging from 2-4% in low risk patients up to 8-40% in high-risk
      patients). Hydration is a mainstay of treatment for acute pancreatitis, independent of
      etiology. Aggressive hydration has also been shown to decrease incidence of PEP. Rectal
      NSAIDs, including Indomethacin, has a proven role in prevention of PEP. Though both
      aggressive hydration and rectal indomethacin are efficacious in preventing PEP, there is no
      head to head trial comparing the efficacy of these two therapeutic modalities. Thus, the aim
      is to determine whether aggressive intravenous peri-procedural hydration or high dose rectal
      indomethacin immediately after ERCP decrease the incidence of PEP. The investigator's
      hypothesis is that prophylactic treatment with aggressive intravenous hydration is not
      inferior to rectal indomethacin in preventing PEP.
    

Detailed description: 
      Endoscopic Retrograde Cholangiopancreatography (ERCP) is a commonly performed endoscopic
      procedure used to treat pancreato-biliary pathology. Acute pancreatitis is the most common
      major complication of (ERCP)[1] which is reported to occur in 2-10% of patients overall
      (ranging from 2-4% in low risk patients up to 8-40% in high-risk patients) [1, 2]. The wide
      range of reported incidence of post-ERCP pancreatitis over risk groups in observational
      studies prompted a 2014 systematic review including 108 RCTs that covered 13 296 patients[3].
      The overall incidence of post-ERCP pancreatitis was 9.7%, of which 8.6% of cases were mildly
      severe, 3.9% were moderate,and 0.8% were severe. The incidence of all-severity post-ERCP
      pancreatitis in high-risk patients was 14.7%. This study also found, however, that the
      incidence of severe post-ERCP pancreatitis (0.5% of all ERCPs performed) did not differ
      between patients in a high-risk subgroup and non-risk-stratified RCTs (0.8% vs. 0.4%,
      respectively), perhaps due to heterogeneity between the RCTs regarding the risk assessment of
      patients

      The generally accepted criteria for the diagnosis of post-ERCP pancreatitis were proposed in
      1991 during a consensus workshop. These criteria include new onset of pancreatic-type
      abdominal pain associated with at least a threefold increase in serum amylase or lipase
      occurring within 24 h after ERCP, and the pain symptoms need to be sufficiently severe to
      require admission to the hospital or to extend the length of stay of patients who are already
      hospitalized [3].

      Hydration is a mainstay of treatment for acute pancreatitis, independent of etiology[4].
      Experiments in animal models demonstrate that pancreatic microvascular hypoperfusion leads to
      necrosis[5]. Clinical studies of fluid resuscitation in patients with acute pancreatitis
      suggest that hemoconcentration and decreased systemic perfusion are associated with increased
      risk of pancreas necrosis and unfavorable outcome [6]. Hydration has also been shown to
      decrease incidence of PEP.

      Besides Hydration, rectal NSAIDS, including Indomethacin, has role in prevention of post ERCP
      Acute pancreatitis. Though both aggressive hydration and rectal indomethacin are efficacious
      in preventing Post ERCP pancreatitis there is no head to head trial comparing the efficacy of
      these two therapeutic modality.

      To determine whether aggressive intravenous peri-procedural hydration or high dose rectal
      indomethacin immediately after ERCP decrease the incidence of post ERCP pancreatitis.

      The investigator's hypothesis is that prophylactic treatment with aggressive intravenous
      hydration is not inferior to rectal indomethacin in protecting against Post ERCP pancreatitis
      .
    

Intervention name(s): Lactated Ringer; Rectal Form Indometacin
Intervention type(s): Drug; Drug
Intervention description(s): High-volume Lactated Ringer Solution; Post-ERCP rectal administration of 100 MG Indomethacin
Other intervention name(s): COMPOUND SODIUM LACTATE INJECTION I.P., INVEN PHARMACEUTICALS PVT.LTD, MP, INDIA; INDOMETHACIN SUPPOSITORY 100 Mg B.P, GALEN PHARMACEUTICAL LTD, GUJRAT, INDIA
Intervention MeSH terms: Indomethacin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective randomized open-label parallel-group non-inferiority controlled clinical trial
Masking: None (Open Label)
Primary purpose: Prevention