This study is a single center pilot, open label randomized-comparative trial, conducted at a tertiary care center in North India. Institutional ethical approval was obtained. The study was conducted in compliance with the Declaration of Helsinki and Good Clinical Practice guidelines. Informed written consent was obtained from all the patients before enrollment in the study. The trial is registered with the Clinical Trials registry-India (CTRI/2018/01/011188).
All the consecutive admitted patients (between 18 and 65 years of age) of moderately severe (MSAP) and severe AP (SAP) of any etiology and within 14 days after the onset of pain were included. The patients who were already started on diet at the time of admission, mild AP, pregnant and lactating women, co-morbid diseases such as chronic liver disease, chronic renal failure or malignancy, and refusal to consent were excluded from the study. Diagnosis and severity of AP was based on revised Atlanta classification.25 All patients underwent blood investigations which includes complete hemogram, liver and kidney function test, serum calcium level, lipid profile and in select group of patient’s serum parathormone level. 5 mL serum was stored for further analysis for pre-albumin, C-reactive (CRP) and transferrin. The patients who required radiological imaging was preferably underwent either ultrasonography (USG) or contrast enhanced computed tomography (CECT) of abdomen, based on treating clinician decision. Along with nutritional intervention, standard medical treatment for AP and support for organ failure was given to the patients as described in detail elsewhere.3
Randomization and allocation concealment
After assessing the eligibility of the patients, they were randomly allocated in two groups: kitchen-based diet (liquid or semisolid or solid diet as per tolerance) (group 1) and exclusive commercial polymeric formulations (group 2). Randomization was done by using computer generated sequence by pseudo random code. Allocation of patients to receive the intervention was done by sequentially numbered opaque sealed envelope (SNOSE) method. Generation of random numbers and preparation of the envelopes was done by a statistician not associated with the conduct of the study.
Interventions and type of feed formulations
Weight-based equation was used to determine energy (25–30 kcal/kg/d) and protein requirements (1.2-2 g/kg/d). Diet was started within 24 hours after inclusion. An attempt was made to increase their caloric intake from 250 kcal/d to nutritional goal (25–30 kcal/kg/d of ideal body weight) in 3–4 days duration. If patient developed pain or intolerance, this was recorded, and diet was stopped; and diet was gradually introduced and increased again when the patient was able to tolerate. The feed in both groups was aimed to be isocaloric (1kcal/ml). Patients were monitored daily for nutrient supply, tolerance, gastrointestinal symptoms, and recurrence of pain. Oral route was preferred for the patients. If oral diet was not tolerated than nasogastric or nasojejunal route was tried to meet the calorie requirement. Duration of intervention was for 14 days.
Kitchen-based diet: Group 1
Kitchen-based diet contains all the constituents from each food group (cereals, pulses, vegetables, milk & milk products, eggs etc). In this group, patients were given kitchen or home-made diet (solid/semisolid/ liquid diet as tolerated). Liquid diet denotes curd or milk-based feed enriched with oil, sugar, and starch (approximate macronutrient composition- carbohydrate: 50%, fat: 32% and protein: 18%). In case of intolerance to regular food, these kitchen-based liquid feeds were additionally given to increase their nutrients intake either through oral route or tube feeding.
Commercial Polymeric formulation: Group 2
A commercially available polymeric enteral formulation (Essential BN/DM, Azzura Pharmaconutrition Pvt. Ltd., Delhi-NCR, India) was used. In case of uncontrolled blood sugar levels, diabetic formula was used. This contains 50–55% complex carbohydrates, 15–20% intact proteins and 30% fats mainly long chain triglycerides.
Study Outcomes and their definitions
To study the effect of kitchen-based diet on refeeding pain, tolerability, infectious complications, length of hospital stay and mortality in moderately severe and severe acute pancreatitis within 14 days of onset of pain compared to commercial polymeric formulation for enteral nutrition.
Refeeding pain was defined as occurrence of pain requiring stopping of feeds.26 The feed/diet was reintroduced slowly once the pain subsided. Abdominal discomfort was not considered to be pain relapse if feeding was continued and tolerated by patients. Feed tolerability was defined as ability to take the prescribed diet without gastrointestinal symptoms bloating, diarrhea, constipation, nausea, and vomiting and aspiration pneumonia complication. Other outcomes measured were infectious complications, duration of hospital and ICU stay, change in serum pre-albumin and serum transferrin. Biochemical parameters (CRP, pre albumin and transferrin) were done at day 1 (initiation of diet) and repeated at day 14. The patients were further followed till discharge or death during hospitalization (Fig. 1). Discontinued were those patients for whom only baseline data were available and outcome measures for 14 days were not available due to various reasons i.e. death (during 14 days of intervention), ileus and protocol violation. (Fig. 1).
Serum pre-albumin was measured with Immunology Consultants Laboratory (Human Prealbumin ELISA kit, USA); whereas serum transferrin was measured by Thermo Scientific (Human Transferrin ELISA kit, USA) and CRP was measured by XEMA Co, Ltd (CRP ultra-EIA ELISA kit, Russia).
Sample size
This was a pilot study, as there is lack of previous studies comparing kitchen-based diet to commercial formulations. Approximately 90–100 patients/year of moderately severe and severe acute pancreatitis got admitted at our institute. Considering > 50% patients to be excluded due to various exclusion criteria we considered to recruit a total of 60 patients in two years.
Changes in protocol after trial commencement
Initially we planned to recruit patients with moderately severe or severe AP presenting within 7 days of onset of pain and planned to recruit 50 patients in each arm. We observed that majority of these patients presented after 7 days of pain onset as our center is a tertiary and referral center. So, we expanded our inclusion criteria to moderately severe or severe AP presenting within 14 days of onset of pain. In initial 8 months of study, we could recruit only 18 patients out of 90 screened patients with acute pancreatitis. Assuming a similar trend, we planned to recruit a total of 60 patients in next one and half year in this pilot study.
Statistical analysis
Data were analyzed using statistical software STATA 14.0. Categorical data were expressed as frequency and percentage. Quantitative data were expressed as mean ± standard deviation or median for variables after normal or skewed distribution, respectively. Chi-square or fisher exact test was used to compare proportion of categorical variable between two groups. Those variables followed normal distribution was compared by independent t test between the groups. Those variables did not follow normal distribution were compared by Rank sum test. P value ≤ 0.05 was considered significant.