Post-ERCP Acute PancreatitisPhase 2/3AHRI-PEPNCT03629600
Trial of Aggressive Hydration Versus Rectal Indomethacin for Prevention of Post-ERCP Pancreatitis
A Phase 2/3 study testing Lactated Ringer and Rectal Form Indometacin in people with Post-ERCP Acute Pancreatitis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post-ERCP Acute Pancreatitis
- What is being tested?
- Lactated Ringer and Rectal Form Indometacin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 352 participants
- Where
- 1 siteIndia
- Study dates
- 15 Oct 2017to 31 May 2018
- Phase
- Phase 2/3
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients aged 18 to 70 years undegoingt ERCP for the first time
- Patients undergoing ERCP for standard clinical indications
Who cannot join
- Ongoing acute pancreatitis
- Known chronic calcific pancreatitis
- Pancreatic head mass
- Any malignancy
- Standard contraindications to ERCP
- Unwillingness or inability to consent for the study
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- Ongoing hypotension including those with sepsis
- Cardiac insufficiency (CI, >NYHA Class II heart failure)
- Renal insufficiency (RI, creatinine clearance <40mL/min)
- Severe liver dysfunction (albumin < 3mg/dL)
- Respiratory insufficiency (defined as oxygen saturation < 90%)
- Greater than 70 years of age
- Pregnancy
- Breastfeeding mother
- Allergy/hypersensitivity to aspirin or NSAIDs
- Received NSAIDs in prior 7 days (aspirin 325mg or less ok)
- Active or recurrent (within 4 weeks) gastrointestinal hemorrhage
- Hyponatremia (Na+ levels < 135mEq/L))
- Hypernatremia (Na+ levels > 150mEq/L) will be excluded.
- Edema or anasarca
- Ascites
- Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas divisum (dorsal duct not attempted on injected)
- ERCP for biliary stent removal or exchange without anticipated pancreatogram
- Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
- Anticipated inability to follow protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Open-label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis (PEP)
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.
Read the 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 .
- Conditions
- Post-ERCP Acute Pancreatitis
- Being tested
- Lactated Ringer, Rectal Form Indometacin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactated RingerDrug
Also called COMPOUND SODIUM LACTATE INJECTION I.P., INVEN PHARMACEUTICALS PVT.LTD, MP, INDIA
High-volume Lactated Ringer Solution
Rectal Form IndometacinDrug
Also called INDOMETHACIN SUPPOSITORY 100 Mg B.P, GALEN PHARMACEUTICAL LTD, GUJRAT, INDIA
Post-ERCP rectal administration of 100 MG Indomethacin
| Study group | Role | What they receive |
|---|---|---|
| Aggressive Hydration | Experimental | Patients randomized to the aggressive intravenous hydration group received Lactated Ringers solution (LR) [COMPOUND SODIUM LACTATE INJECTION I.P.,INVEN PHARMACEUTICALS PVT.LTD,MP,INDIA] intravenously (IV) at 3 mL/kg/hr during the ERCP, a 20cc/kg IV bolus immediately afterward, and then at 3 mL/kg/hr for 8 hours following the procedure. Receives: Drug: Lactated Ringer |
| Rectal Indomethacin | Active comparator | Patients randomised to Rectal Indomethacin were administered a suppository of 100 mg of indomethacin [Indomethacin Suppository 100 Mg B.P, GALEN PHARMACEUTICAL LTD, GUJRAT, INDIA] just after the completion of ERCP procedure. Receives: Drug: Rectal Form Indometacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-ERCP Acute Pancreatitis
The primary endpoint is development of post-ERCP pancreatitis (PEP, a categorical variable) which will be defined as presence of increased abdominal pain and a serum amylase level three times the upper limit of normal (3xULN). Increased pain will be defined as an increase in the visual analog pain score compared to the value immediately prior to ERCP
Measured: 24 hours
Secondary outcomes (3)
Clinical volume overload
Clinical volume overload was defined by physical findings of lower extremity edema and pulmonary rales.
Measured: 24 hours
Serum Amylase three times the upper limit of normal
Serum amylase three times the upper limit of normal is a secondary outcome measure. (Measured with α-Amylase KIT by direct substrate method; BEACON DIAGNOSTICS PVT LTD, INDIA)
Measured: 8 hours
Post-ERCP pain abdomen: VAS
Patients admitted with pain abdomen after ERCP for less than 24 hrs. Increased abdominal pain is defined as an increase in abdominal pain based on the visual analogue score following the ERCP compared to the score immediately prior to the ERCP.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start15 Oct 2017
- Primary completion15 Feb 2018
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-ERCP Acute PancreatitisStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized open-label parallel-group non-inferiority controlled clinical trial
- Masking
- None (open label)
- Enrolment
- 352 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kshaunish Das, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Kshaunish Das, MD, DM, Principal investigator, Professor, Division of Gastroenterology, SDLD, IPGMER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03629600
- Sponsor's protocol ID
- IEC/2016/396
- Acronym
- AHRI-PEP
- Status last verified
- Aug 2018
- First submitted
- 9 Aug 2018
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Baseline data, outcomes
Publications
Guha P, Patra PS, Misra D, Ahammed SM, Sarkar R, Dhali GK, Ray S, Das K. An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP). J Clin Gastroenterol. 2023 May-Jun 01;57(5):524-530. doi: 10.1097/MCG.0000000000001712. Epub 2022 Apr 21.
PubMed 35470300
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Open-label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis (PEP)
- ClinicalTrials.gov ID
- NCT03629600
- Acronym / sponsor ID
- AHRI-PEP / IEC/2016/396
- Conditions
- Post-ERCP Acute Pancreatitis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 352 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 15 Oct 2017 (actual)
- Primary completion
- 15 Feb 2018 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 14 Aug 2018 (actual)
- 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.
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 .
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective randomized open-label parallel-group non-inferiority controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Aggressive Hydration | Experimental | Drug: Lactated RingerPatients randomized to the aggressive intravenous hydration group received Lactated Ringers solution (LR) [COMPOUND SODIUM LACTATE INJECTION I.P.,INVEN PHARMACEUTICALS PVT.LTD,MP,INDIA] intravenously (IV) at 3 mL/kg/hr during the ERCP, a 20cc/kg IV bolus immediately afterward, and then at 3 mL/kg/hr for 8 hours following the procedure. |
| Rectal Indomethacin | Active comparator | Drug: Rectal Form IndometacinPatients randomised to Rectal Indomethacin were administered a suppository of 100 mg of indomethacin [Indomethacin Suppository 100 Mg B.P, GALEN PHARMACEUTICAL LTD, GUJRAT, INDIA] just after the completion of ERCP procedure. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- All patients aged 18 to 70 years undegoingt ERCP for the first time
- Patients undergoing ERCP for standard clinical indications
Key exclusion criteria (25 listed)
- Ongoing acute pancreatitis
- Known chronic calcific pancreatitis
- Pancreatic head mass
- Any malignancy
- Standard contraindications to ERCP
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 |
|---|---|---|
| Lactated RingerAlso: COMPOUND SODIUM LACTATE INJECTION I.P., INVEN PHARMACEUTICALS PVT.LTD, MP, INDIAHigh-volume Lactated Ringer Solution | Drug | Aggressive Hydration |
| Rectal Form IndometacinAlso: INDOMETHACIN SUPPOSITORY 100 Mg B.P, GALEN PHARMACEUTICAL LTD, GUJRAT, INDIAPost-ERCP rectal administration of 100 MG Indomethacin | Drug | Rectal Indomethacin |
Primary outcome
Post-ERCP Acute Pancreatitis
Time frame: 24 hours
The primary endpoint is development of post-ERCP pancreatitis (PEP, a categorical variable) which will be defined as presence of increased abdominal pain and a serum amylase level three times the upper limit of normal (3xULN). Increased pain will be defined as an increase in the visual analog pain score compared to the value immediately prior to ERCP
3 secondary outcomes
Clinical volume overload
Time frame: 24 hours
Serum Amylase three times the upper limit of normal
Time frame: 8 hours
Post-ERCP pain abdomen: VAS
Time frame: 24 hours
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 16 Aug 2018.
- Derived from this study: PubMed 35470300Guha P, Patra PS, Misra D, Ahammed SM, Sarkar R, Dhali GK, Ray S, Das K. An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP). J Clin Gastroenterol. 2023 May-Jun 01;57(5):524-530. doi: 10.1097/MCG.0000000000001712. Epub 2022 Apr 21.
- Individual participant dataSharing planned: Undecided. Baseline data, outcomes
Related trials for Post-ERCP Acute Pancreatitis
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Cold and NSAID Trial for Prevention of Post-ERCP Pancreatitis
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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.
Kshaunish Das, MD, DM principal investigator
Professor, Division of Gastroenterology, SDLD, IPGMER
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Lactated Ringer and Rectal Form Indometacin in people with Post-ERCP Acute Pancreatitis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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 2 inclusion and 25 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 16 Aug 2018. 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 India. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Post-ERCP Acute Pancreatitis (time frame: 24 hours). 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 NCT03629600, which also lists 1 linked publication.
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 16 Aug 2018.