Clinical trial NCT04168801: Early Oral Refeeding in Mild Acute Pancreatitis
Official title: Non-inferiority Comparative Clinical Trial Between Early Oral Refeeding Versus Usual Oral Refeeding in Mild Acute Pancreatitis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pancreatitis
Keywords: Mild acute pancreatitis
Oral refeeding
Non inferiority clinical trial
Lead sponsor: Hospital Regional de Alta Especialidad del Bajio
Sponsor class: OTHER
First posted: 2019-11-19
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prior authorization from the ethics committee in health research. Patients with diagnosis of mild acute biliary pancreatitis, were divided into: Group A (early oral refeeding) and Group B (usual oral refeeding). Outcome measures were lipase pancreatic, systemic inflammatory response (concentrations of leukocytes) were used as marker for it, feasibility evaluated by abdominal pain recurrence, presence and recurrence of gastrointestinal symptoms and length of hospital stay.
Primary purpose: TREATMENT

Brief summary: Background The aim of the study is to compare the onset of oral feeding in the first 24 hours after hospital admission and determine if this influences the recurrence of pain or alters the blood levels of pancreatic enzymes, compared to usual oral refeeding in patients with mild acute pancreatitis Methods This Non-Inferiority Randomized controlled trial was carried out between September 2018 and June 2019, prior authorization from the ethics committee in health research. Patients with diagnosis of mild acute biliary pancreatitis, were divided into: Group A (early oral refeeding) and Group B (usual oral refeeding). Outcome measures were lipase pancreatic, systemic inflammatory response (concentrations of leukocytes) were used as marker for it, feasibility evaluated by abdominal pain recurrence, presence and recurrence of gastrointestinal symptoms and length of hospital stay. The aim of the present study is to compare the onset of oral feeding in the first 24 hours after hospital admission and determine if this influences the recurrence of pain or alters the blood levels of pancreatic enzymes, compared to usual oral refeeding in patients with mild acute pancreatitis.

Detailed description: BACKGROUND Acute pancreatitis (AP) is an inflammatory pancreatic process, presents different severity degrees \[1\]. Over the last two decades, there has been a paradigm shift in the management, from surgical to "step up" approach using percutaneous or endoscopic catheter drainage followed by minimally invasive necrosectomy \[2\]. As no curative therapy is currently available for AP, early treatment consists of supportive care which includes adequate fluid resuscitation, pain management and enteral nutrition \[3\]. Pancreatic rest by Nil Per Oral (NPO) strategy was considered necessary in AP till abdominal pain get resolved and the levels of pancreatic and inflammatory markers decrease \[4\]. This trend has changed, now it is clear that the early oral refeeding for PA mild does not only provide adequate caloric intake, it may also improve clinical outcomes. It has been hypothesized that the combination of disturbed intestinal motility, microbial overgrowth and increased permeability of the gut can lead to bacterial translocation, thus causing infection of pancreatic necrosis \[5,6\].

The oral refeeding (OR) may reduce translocation by stimulating intestinal motility, reducing bacterial overgrowth and thereby maintaining mucosal gut integrity \[7,8\]. Also decrease infection complications, organ failure and mortality as compared with routine total parenteral nutrition \[9,10\]. In patients with (predicted) mild pancreatitis, numerous studies concluded that a normal oral diet can be resumed once the pain is decreasing \[11-13\], However, it remains unclear what the optimal time to do it is. There is still no consensus about the definition of "early" refeeding.

The aim of the present study is to compare the onset of oral feeding in the first 24 hours after hospital admission and determine if this influences the recurrence of pain or alters the blood levels of pancreatic enzymes, compared to usual oral refeeding in patients with mild acute pancreatitis.

METHODS

Patients This Randomized controlled trial was carried out between September 2018 and June 2019, prior authorization from the ethics committee in health research.

A total number of 124 patients were randomized in this study. The sample size was calculated according to the formula published by Bouemn et all 2015 \[14\], in which a percentage of success was estimated with the standard treatment of 90% compared to the experimental management of 85%, with a margin of no less than 10%, with an alpha for a tail of 0.05%, and a beta of 20 %, with a percentage of estimated losses of approximately 10%, a total of 62 patients per group was obtained.

Definitions The diagnosis of AP was established when the patient presents two or more of the following three findings: typical abdominal pain, elevation of serum pancreatic enzymes (amylase and/or lipase) at more than three times the upper limit of the normal value, and imaging study (ultrasonography or computed tomography) suggestive of AP \[15\].

Severity Assessment Severity assessment of AP was done based on the revised Atlanta classification into mild, moderately severe and severe. Absence of organ failure or local or systemic complications was labelled as mild AP; of was defined using the modified Marshall scoring system \[16\]; and only the patients whose complete these severity criteria were randomized for the study.

Protocol Once the diagnosis of acute biliary pancreatitis was confirmed and the course was mild, corresponding informed consent signed.

Fluid therapy with crystalloid solution (Hartmann), initial bolus of 10 mL / kg and followed by infusion for 24 h of 1.5 mL / kg / h.

Pain management with opioid weak tramadol 50mg every 6 hours and paracetamol 1 gram every 8 hours with continuous evaluation of the analogue numerical scale to determine the need for extra doses

Type of Diet:

In both groups, their initial diet was the same so that this did not influence the results to be measured.

The soft diet consisted of one of 900 Kcal per day, with 86.7% carbohydrates (190 g), 13.3% protein (30 g) and 0% lipids (0 g); during 24 h.

When the diet was adequately tolerated and there was no evidence of clinical complications or deterioration, normal diet was indicated, and the follow-up continues.

Data Collection:

Laboratorial data, such as leukocytes, amylase and lipase were collected after inclusion in the study and after 24 and 48 h of oral refeeding. Clinical data records include age, gender, time from onset of pain baseline, Marshall score at admission and after start the oral feeding, gastrointestinal symptoms, abdominal pain, days until solid food intake, pain relapse, complications, length of hospital stay and readmissions.

Statistical analysis Date are presented as frequency and percentage, comparisons between groups were using the χ2 test for binary data or Fisher´s exact test. Continuous variables are presented as median and range interquartile range and were compared using the Mann-Whitney U-test or t student test if they meet normal criteria. p-Values of less than 0.05 were considered significant. Statistical analyses were performed with SPSS version 25.0.0. Analysis by intention to treat was used.

Eligibility criteria: Inclusion Criteria:

* All patients admitted to the surgery services with diagnosis of acute biliary pancreatitis
* Whit mild episode criteria and symptom onset time less than 24 hours

Exclusion Criteria:

* Patients with pancreatitis from another cause other than biliary
* Pregnant
* History of chronic pancreatitis
* Under 18 or over 75 years
* With moderately severe or severe acute biliary pancreatitis

Primary outcomes:
measure: abdominal pain recurrence
timeFrame: 72 hours
Secondary outcomes:
measure: systemic inflammatory response
timeFrame: 72 hours
Other outcomes:
Locations:
city: Leon
country: Mexico
facility: Hospital Regional de Alta Especilidad del bajio
state: Guanajuato
Study officials:
affiliation: Hospital Regional de Alta Especialidad
name: Edgard Lozada, Dr
role: PRINCIPAL_INVESTIGATOR
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