A Randomized Controlled Trial evaluating efficacy of Intravenous Albumin Infusion with Corticosteroids and Exclusive Enteral Nutrition (EEN) versus Corticosteroids and EEN alone in patients with Acute Severe Ulcerative Colitis

Acute severe ulcerative colitis (ASUC) is a medical emergency which complicates the course of Ulcerative Colitis in up to 20-25% of patients. ASUC is defined according to the modified Truelove and Witts criteria, combining a bloody stool frequency >/= 6/day with at least one sign of systemic toxicity such as pulse rate >90 bpm, temperature > 37.8 C, hemoglobin < 10.5 g/dl and/or an ESR > 30 mm/h. Corticosteroids remain first line therapy for ASUC, with a pooled response rate of 67% and colectomy rate of around 30%. Rescue therapies including ciclosporin and infliximab are costly and are associated with significant side effects, many patients either cannot afford them or are not fit for these therapies. Surgery again, in emergency settings is associated with significant morbidity, and higher mortality than elective setting. So, there is an unmet need for low cost, safe and effective therapies which can augment the response to steroids . In a recent study at our center, we demonstrated the efficacy of 1-week exclusive enteral nutrition (EEN) in improving the response to IV steroids. The possible mechanisms for such an improvement could be the anti-inflammatory and gut microbiota modulating properties of EEN. However, improvement in nutritional parameters and serum albumin concentrations could also be responsible. Furthermore, several studies have suggested a low baseline albumin level as a predictor of non-response to steroids. Albumin has pleotropic properties including anti-oxidant and anti-inflammatory actions. Hence a combination of two approaches- EEN, acting at the tissue level (through its microbiota modulating and epithelial barrier improving properties) and intravenous albumin at systemic level (through its anti-inflammatory properties) could further improve the response to IV steroids. So, in this study we will evaluate the role of intravenous albumin infusion along with steroid therapy and EEN in ASUC.

This study will be conducted as an open labelled, randomized controlled trial where patients of ASUC will be randomized in a 1:1 ratio to receive either IV albumin infusion + EEN + standard of care or standard of care + EEN. All patients will be treated with intravenous hydrocortisone (400 mg/day) along with other standard treatment. EEN will be provided to all the patients in both the groups. EEN will be provided with semi-elemental protein-based formula peroral or through nasogastric tube if needed for 7 days. Patients in the intervention group in addition will be provided with 20% w/v intravenous albumin solution (100 ml) i.e. 20 g/day which will be infused over 3-4 hours for a total duration of 5 days. The primary outcome measure will be to look for proportion of patients with steroid failure and treatment related adverse events in both the groups. The secondary outcome measures will include response rates to IFX rescue therapy in both the groups, if IV steroids are failing; changes in fecal calprotectin and serum CRP level after 3rd day of treatment in both the groups; changes in ischemia modified albumin, albumin fractions (HMA, HNA1 and HNA2) and pro-inflammatory cytokines (IL6 and TNF alpha) at day 5 in both the groups, and duration of hospital stay in both the groups