Preventing the Recurrence of Acute Pancreatitis by Alcohol and Smoking Cessation (REAPPEAR)

Recurrent Acute Pancreatitis Prevention by the Elimination of Alcohol and Cigarette Smoking (REAPPEAR): Protocol of a Randomized Controlled Trial and a Cohort Study

Recurrence of acute pancreatitis (AP) is often facilitated by regular alcohol consumption and smoking. An applied lifestyle intervention focusing on the cessation of alcohol consumption and smoking might prevent the recurrence of AP. REAPPEAR Study is a randomized controlled trial and a cohort study focusing on the efficacy of the lifestyle intervention and the effect of quitting alcohol and smoking respectively.

Alcohol and smoking caused recurrent acute pancretitis might be prevented. The condition is known for it's causative effect of chronic pancreatitis and nonbeneficial effect on quality of life. Clinical equipoise regarding the impact of alcohol and smoking cessation still exists, due to the non existence of well designed clinical trials. The aim of the REAPPEAR study is to investigate the effect of cessation program of alcohol and tobacco use on the recurrence of acute pancreatitis. The REAPPEAR Study is a combined clinical trial involving a randomized multicenter clinical trial (REAPPEAR-T), which assesses the effect of the cessation program on the recurrence of the acute pancreatitis, and a cohort analysis, which investigates the effect of smoking and alcohol cessation on the recurrance of acute pancreatitis. Daily smokers, hospitalized with alcohol-induced pancreatitis will be included in the trial. Standard cessational intervention will be provided for all patients before enrollment. Laboratory testing, measurement of blood pressure and BMI will be performed, while also hair, urine samples and blood will be retrieved for later biomarker measurement. The evaluation of motivation to change, addiction, quality of life and socioeconomic status will be recorded at every visit, which will take place every 3 months or yearly according to the random allocation. For patients, who present at visit of every 3 months a brief intervention will be provided, together with a laboratory testing to provide feedback. The primary composite endpoint of this study will be the recurrence rate of acute pancreatitis irrespective of etiology and all-cause mortality in a 2 year timeframe. The cost-effectiveness will be also evaluated.

The assessors of the outcomes will be blinded regarding allocation. The medical team providing the visits and treatment during hospitalization rwill not be aware of the allocation. Patients and the study nurse can not be blinded, due to the nature of the intervention.

Standard intervention (SI) will be a part of standard care in all participating centers, and will be provided for all acute pancreatitis patients, who are hospitalized and their condition is alcohol induced. A specially trained study nurse will deliver the intervention, since they were found to be the most effective regarding the decrease in alcohol consumption and smoking. The cost- effectiveness of the intervention and the feasibility were also taken into account. The Assist-linked brief intervention according to the World Health Organization (WHO) will serve as the base for the intervention, with an avarage of 30 minutes, based on a review containing 69 randomized controlled trials, which concluded that longer intervention do not have additional benefit. The patients will be also educated about the disease course of acute pancreatitis during the standard intervention.

Standard intervention (SI) will be performed as described above. The repeated intervention will be delivered by the former mentioned same nurse and will be structured similarly to the standard intervention. Every visit and intervention will be individually altered according to the motivation of the patient, but they will follow the same structure. The sessions can be divided into three main parts: first, highlighting the harmful effects of smoking and alcohol on the pancreatic functions. Secondly, a discussion about the motivation of the patient will happen. The last portion of the session will focus on the responsibility of the individual to reach the desired goal will be highlighted. To enhance the efficacy of our intervention we wish to provide feed-back for the patient based on laboratory testing: the mean corpuscular volume (MCV) and gamma glutamyl-transferase (GGT) values will be measured right before the interview. The study nurse will not take part in patient care.

Recurrence rate of AP irrespective of etiology and all cause mortality. The diagnosis of AP based on the two out of three rule. (At least 2 of 3 typical features are present -upper abdominal pain, elevation of serum pancreatic enzymes at least 3 times the reference value, and imaging findings consistent with AP.)

Recurrence of acute pancreatitis irrespective of etiology given as cumulative incidence and as rate of event

Likely pancreatitis, fulfilling the diagnostic criteria of epigastric pain, a serum amylase or lipase level at least two times the upper normal level, and elevated leukocyte count or CRP levels

Change of alcohol consumption compared to baseline given in gram per week based on patient reported data

Change of tobacco use compared to the baseline given in pieces per day based on patient reported data

Inclusion criteria: Patient hospitalized with alcohol-induced AP (defined by the revised Atlanta criteria 38) Every day smoker (defined as an adult patient who smoked at least 100 cigarettes in his or her lifetime, and now smokes on a daily basis; as per the CDC definition), with at least 1-year history of smoking Aged 18-80 years Provided written informed consent Willing to participate in the intervention in every three months Exclusion criteria: Possible etiologies for AP other than alcohol (eg. gallstone-related, hypertriglyceridemia above 11.5 mM 40-42, hypercalcemia, viral infection) if the etiological cannot be terminated during the index admission (lack of same admission cholecystectomy, familiar hypertrygliceridemia) and cases with combined etiological factors will be excluded Untreated, decompensated or severe mMajor psychiatric illnesses (e.g. schizophrenia, bipolar disorder, dementia) Currently taking part in a smoking cessation program Undergoing active or palliative treatment for malignancy Pregnancy, breastfeeding Life expectancy is less than two years Didn't agreed to participate Other

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