Re current acute pancreatitis prevention by the elimination of alcohol and ciga r ette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study

Klementina Ocskay, Márk Félix Juhász, Nelli Farkas, Noémi Zádori, Lajos Szakó, Zsolt Szakács, Andrea Szentesi, Bálint Erőss, Emőke Miklós, Antal Zemplényi, Béla Birkás, Árpád Csathó, István Hartung, Tamás Nagy, László Czopf, Ferenc Izbéki, László Gajdán, Mária Papp, László Czakó, Dóra Illés, Marco V Marino, Antonello Mirabella, Ewa Małecka-Panas, Hubert Zatorski, Yaroslav Susak, Kristina Opalchuk, Gabriele Capurso, Laura Apadula, Cristian Gheorghe, Ionut Adrian Saizu, Ole H Petersen, Enrique de-Madaria, Jonas Rosendahl, Andrea Párniczky, Péter Hegyi, Hungarian Pancreatic Study Group, Klementina Ocskay, Márk Félix Juhász, Nelli Farkas, Noémi Zádori, Lajos Szakó, Zsolt Szakács, Andrea Szentesi, Bálint Erőss, Emőke Miklós, Antal Zemplényi, Béla Birkás, Árpád Csathó, István Hartung, Tamás Nagy, László Czopf, Ferenc Izbéki, László Gajdán, Mária Papp, László Czakó, Dóra Illés, Marco V Marino, Antonello Mirabella, Ewa Małecka-Panas, Hubert Zatorski, Yaroslav Susak, Kristina Opalchuk, Gabriele Capurso, Laura Apadula, Cristian Gheorghe, Ionut Adrian Saizu, Ole H Petersen, Enrique de-Madaria, Jonas Rosendahl, Andrea Párniczky, Péter Hegyi, Hungarian Pancreatic Study Group

Abstract

Background/objectives: Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP.

Methods and analysis: The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort.

Ethics and dissemination: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals.

Trial registration number: NCT04647097.

Keywords: pancreatic disease; preventive medicine; substance misuse.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
SPIRIT flow chart. Standard intervention will be provided for every patient as part of standard therapy. All randomised participants will be included in the REAPPEAR-T (trial) and REAPPEAR-C (cohort) as well. After reaching the required patient numbers for the REAPPEAR-T, further patients will be enrolled to the REAPPEAR-C in accordance with the estimated sample size. AP, acute pancreatitis. SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials, REAPPEAR, Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking.
Figure 2
Figure 2
SPIRIT time table. SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials; BMI, body mass index; BP, blood pressure; CG; control group, CP; cessation programme, HR; heart rate.

References

    1. Wadhwa V, Patwardhan S, Garg SK, et al. . Health care utilization and costs associated with acute pancreatitis. Pancreas 2017;46:410–5. 10.1097/MPA.0000000000000755
    1. Szentesi A, Tóth E, Bálint E, et al. . Analysis of research activity in gastroenterology: pancreatitis is in real danger. PLoS One;11:e0165244. 10.1371/journal.pone.0165244
    1. Machicado JD, Yadav D. Epidemiology of recurrent acute and chronic pancreatitis: similarities and differences. Dig Dis Sci 2017;62:1683–91. 10.1007/s10620-017-4510-5
    1. Tenner S, Baillie J, DeWitt J, et al. . American College of gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400–15. 10.1038/ajg.2013.218
    1. Guda NM, Muddana V, Whitcomb DC, et al. . Recurrent acute pancreatitis: international state-of-the-science conference with recommendations. Pancreas 2018;47:653–66. 10.1097/MPA.0000000000001053
    1. Coté GA, Yadav D, Abberbock JA, et al. . Recurrent acute pancreatitis significantly reduces quality of life even in the absence of overt chronic pancreatitis. Am J Gastroenterol 2018;113:906–12. 10.1038/s41395-018-0087-7
    1. Yadav D, O'Connell M, Papachristou GI. Natural history following the first attack of acute pancreatitis. Am J Gastroenterol 2012;107:1096–103. 10.1038/ajg.2012.126
    1. Mandalia A, Wamsteker E-J, DiMagno MJ. Recent advances in understanding and managing acute pancreatitis. F1000Res 2018;7. 10.12688/f1000research.14244.1. [Epub ahead of print: 28 06 2018].
    1. Krishna SG, Kamboj AK, Hart PA, et al. . The changing epidemiology of acute pancreatitis hospitalizations: a decade of trends and the impact of chronic pancreatitis. Pancreas 2017;46:482–8. 10.1097/MPA.0000000000000783
    1. Nikkola J, Räty S, Laukkarinen J, et al. . Abstinence after first acute alcohol-associated pancreatitis protects against recurrent pancreatitis and minimizes the risk of pancreatic dysfunction. Alcohol Alcohol 2013;48:483–6. 10.1093/alcalc/agt019
    1. Magnusdottir BA, Baldursdottir MB, Kalaitzakis E, et al. . Risk factors for chronic and recurrent pancreatitis after first attack of acute pancreatitis. Scand J Gastroenterol 2019;54:87–94. 10.1080/00365521.2018.1550670
    1. Nikkola J, Laukkarinen J, Lahtela J, et al. . The long-term prospective follow-up of pancreatic function after the first episode of acute alcoholic pancreatitis: recurrence predisposes one to pancreatic dysfunction and pancreatogenic diabetes. J Clin Gastroenterol 2017;51:183–90. 10.1097/MCG.0000000000000564
    1. Nordback I, Pelli H, Lappalainen-Lehto R, et al. . The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial. Gastroenterology 2009;136:848–55. 10.1053/j.gastro.2008.11.044
    1. Lappalainen-Lehto R, Koistinen N, Aalto M, et al. . Goal-related outcome after acute alcohol-pancreatitis -- a two-year follow-up study. Addict Behav 2013;38:2805–9. 10.1016/j.addbeh.2013.07.008
    1. Tolstrup JS, Kristiansen L, Becker U, et al. . Smoking and risk of acute and chronic pancreatitis among women and men: a population-based cohort study. Arch Intern Med 2009;169:603–9. 10.1001/archinternmed.2008.601
    1. Lindkvist B, Appelros S, Regnér S, et al. . A prospective cohort study on risk of acute pancreatitis related to serum triglycerides, cholesterol and fasting glucose. Pancreatology 2012;12:317–24. 10.1016/j.pan.2012.05.002
    1. Sadr-Azodi O, Andrén-Sandberg Å, Orsini N, et al. . Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study. Gut 2012;61:262–7. 10.1136/gutjnl-2011-300566
    1. Majumder S, Gierisch JM, Bastian LA. The association of smoking and acute pancreatitis: a systematic review and meta-analysis. Pancreas 2015;44:540–6. 10.1097/MPA.0000000000000301
    1. Schuckit MA. Alcohol-use disorders. The Lancet 2009;373:492–501. 10.1016/S0140-6736(09)60009-X
    1. Peris P, Parés A, Guañabens N, et al. . Bone mass improves in alcoholics after 2 years of abstinence. J Bone Miner Res 1994;9:1607–12. 10.1002/jbmr.5650091014
    1. Aguilera MT, de la Sierra A, Coca A, et al. . Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring. Hypertension 1999;33:653–7. 10.1161/01.hyp.33.2.653
    1. Seitz HK, Bataller R, Cortez-Pinto H, et al. . Alcoholic liver disease. Nat Rev Dis Primers 2018;4:16. 10.1038/s41572-018-0014-7
    1. Jandíková H, Dušková M, Stárka L. The influence of smoking and cessation on the human reproductive hormonal balance. Physiol Res 2017;66:S323–31. 10.33549/physiolres.933724
    1. Taylor DH, Hasselblad V, Henley SJ, et al. . Benefits of smoking cessation for longevity. Am J Public Health 2002;92:990–6. 10.2105/AJPH.92.6.990
    1. Párniczky A, Kui B, Szentesi A, et al. . Prospective, multicentre, nationwide clinical data from 600 cases of acute pancreatitis. PLoS One 2016;11:e0165309. 10.1371/journal.pone.0165309
    1. Szücs Ákos, Marjai T, Szentesi A, et al. . Chronic pancreatitis: multicentre prospective data collection and analysis by the Hungarian pancreatic study group. PLoS One 2017;12:e0171420. 10.1371/journal.pone.0171420
    1. Weinberger AH, Platt J, Jiang B, et al. . Cigarette smoking and risk of alcohol use relapse among adults in recovery from alcohol use disorders. Alcohol Clin Exp Res 2015;39:1989–96. 10.1111/acer.12840
    1. Yardley MM, Mirbaba MM, Ray LA. Pharmacological options for smoking cessation in heavy-drinking smokers. CNS Drugs 2015;29:833–45. 10.1007/s40263-015-0284-5
    1. Mirbaba M. Heavy-Drinking smokers: pathophysiology and pharmacologic treatment options. Am J Psychiatry Resid J 2016;11:8–11. 10.1176/appi.ajp-rj.2016.110603
    1. Fucito LM, Hanrahan TH. Heavy-Drinking smokers' treatment needs and preferences: a mixed-methods study. J Subst Abuse Treat 2015;59:38–44. 10.1016/j.jsat.2015.07.001
    1. McKelvey K, Thrul J, Ramo D. Impact of quitting smoking and smoking cessation treatment on substance use outcomes: an updated and narrative review. Addict Behav 2017;65:161–70. 10.1016/j.addbeh.2016.10.012
    1. Toll BA, Martino S, O'Malley SS, et al. . A randomized trial for hazardous drinking and smoking cessation for callers to a quitline. J Consult Clin Psychol 2015;83:445–54. 10.1037/a0038183
    1. Crockett SD, Wani S, Gardner TB, et al. . American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology 2018;154:1096–101. 10.1053/j.gastro.2018.01.032
    1. Working Group IAP/APA Acute Pancreatitis Guidelines . IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013;13:e1–15. 10.1016/j.pan.2013.07.063
    1. Samarasekera E, Mahammed S, Carlisle S, et al. . Pancreatitis: summary of NICE guidance. BMJ 2018;362:k3443. 10.1136/bmj.k3443
    1. Isaji S, Takada T, Mayumi T, et al. . Revised Japanese guidelines for the management of acute pancreatitis 2015: revised concepts and updated points. J Hepatobiliary Pancreat Sci 2015;22:433–45. 10.1002/jhbp.260
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. . Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586. 10.1136/bmj.e7586
    1. Banks PA, Bollen TL, Dervenis C, et al. . Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102–11. 10.1136/gutjnl-2012-302779
    1. Yadav D. Reassessing the risk of pancreatitis with alcohol. Pancreas 2016;45:781–2. 10.1097/MPA.0000000000000668
    1. Mosztbacher D, Hanák L, Farkas N, et al. . Hypertriglyceridemia-induced acute pancreatitis: a prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases. Pancreatology 2020;20:608–16. 10.1016/j.pan.2020.03.018
    1. Zádori N, Gede N, Antal J, et al. . Early elimination of fatty acids in hypertriglyceridemia-induced acute pancreatitis (ELEFANT trial): protocol of an open-label, multicenter, adaptive randomized clinical trial. Pancreatology 2020;20:369–76. 10.1016/j.pan.2019.12.018
    1. Szentesi A, Párniczky A, Vincze Áron, et al. . Multiple hits in acute pancreatitis: components of metabolic syndrome synergize each other's deteriorating effects. Front Physiol 2019;10:1202. 10.3389/fphys.2019.01202
    1. Hegyi P, Erőss B, Mátrai P, et al. . The first definition for early chronic pancreatitis. Pancreatology 2018;18:S172. 10.1016/j.pan.2018.05.464
    1. Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. . United European gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J 2017;5:153–99. 10.1177/2050640616684695
    1. Platt L, Melendez-Torres GJ, O'Donnell A, et al. . How effective are brief interventions in reducing alcohol consumption: do the setting, practitioner group and content matter? Findings from a systematic review and metaregression analysis. BMJ Open 2016;6:e011473. 10.1136/bmjopen-2016-011473
    1. WHO ASSIST Working Group . The alcohol, smoking and substance involvement screening test (assist): development, reliability and feasibility. Addiction 2002;97:1183–94. 10.1046/j.1360-0443.2002.00185.x
    1. Kaner EF, Beyer FR, Muirhead C, et al. . Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database Syst Rev 2018;2:CD004148. 10.1002/14651858.CD004148.pub4
    1. Kristenson H, Öhlin H, Hultén-Nosslin MB, et al. . Identification and intervention of heavy drinking in middle-aged men: results and follow-up of 24-60 months of long-term study with randomized controls. Alcohol Clin Exp Res 1983;7:203–9. 10.1111/j.1530-0277.1983.tb05441.x
    1. Pelli H, Lappalainen-Lehto R, Piironen A, et al. . Risk factors for recurrent acute alcohol-associated pancreatitis: a prospective analysis. Scand J Gastroenterol 2008;43:614–21. 10.1080/00365520701843027
    1. Kim S, Apelberg BJ, Avila-Tang E, et al. . Utility and cutoff value of hair nicotine as a biomarker of long-term tobacco smoke exposure, compared to salivary cotinine. Int J Environ Res Public Health 2014;11:8368–82. 10.3390/ijerph110808368
    1. Andresen-Streichert H, Müller A, Glahn A, et al. . Alcohol biomarkers in clinical and forensic contexts. Dtsch Arztebl Int 2018;115:309–15. 10.3238/arztebl.2018.0309
    1. Mikó A, Erőss B, Sarlós P, et al. . Observational longitudinal multicentre investigation of acute pancreatitis (GOULASH plus): follow-up of the GOULASH study, protocol. BMJ Open 2019;9:e025500. 10.1136/bmjopen-2018-025500
    1. Márta K, Szabó AN, Pécsi D, et al. . High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial. BMJ Open 2017;7:e015874. 10.1136/bmjopen-2017-015874
    1. Párniczky A, Mosztbacher D, Zsoldos F, et al. . Analysis of pediatric pancreatitis (apple trial): Pre-Study protocol of a multinational prospective clinical trial. Digestion 2016;93:105–10. 10.1159/000441353
    1. Párniczky A, Abu-El-Haija M, Husain S, et al. . EPC/HPSG evidence-based guidelines for the management of pediatric pancreatitis. Pancreatology 2018;18:146–60. 10.1016/j.pan.2018.01.001
    1. Hritz I, Czakó L, Dubravcsik Z, et al. . [Acute pancreatitis. Evidence-based practice guidelines, prepared by the Hungarian Pancreatic Study Group]. Orv Hetil 2015;156:244–61. 10.1556/OH.2015.30059
    1. Gholam PM. Prognosis and prognostic scoring models for alcoholic liver disease and acute alcoholic hepatitis. Clin Liver Dis 2016;20:491–7. 10.1016/j.cld.2016.02.007
    1. Hedman L, Katsaounou PA, Filippidis FT, et al. . Receiving support to quit smoking and quit attempts among smokers with and without smoking related diseases: findings from the EUREST-PLUS ITC Europe surveys. Tob Induc Dis 2018;16:A14. 10.18332/tid/102787
    1. Saunders JB, Aasland OG, Babor TF, et al. . Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on early detection of persons with harmful alcohol consumption--II. Addiction 1993;88:791–804. 10.1111/j.1360-0443.1993.tb02093.x
    1. Németh Z, Urbán R, Farkas J, et al. . Hungarian adaptation of the long and the short form of the drinking motives questionnaire (DMQ-R). Magyar Pszichológiai Szemle 2012;67:673–94. 10.1556/mpszle.67.2012.4.3
    1. Kuntsche E, Kuntsche S. Development and validation of the drinking motive questionnaire revised short form (DMQ-R SF). J Clin Child Adolesc Psychol 2009;38:899–908. 10.1080/15374410903258967
    1. Heatherton TF, Kozlowski LT, Frecker RC, et al. . The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br J Addict 1991;86:1119–27. 10.1111/j.1360-0443.1991.tb01879.x
    1. Capacities HMoH Az emberi erőforrások minisztériuma egészségügyi szakmai irányelve a dohányzásról való leszokás támogatásáról. Available:
    1. Varga L. Segítségnyújtás kockázatos ivók számára, 2006. National addiction Institute
    1. Petersen OH, Sutton R. Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee. Trends Pharmacol Sci 2006;27:113–20. 10.1016/j.tips.2005.12.006
    1. Rencz F, Gulácsi L, Drummond M, et al. . EQ-5D in central and eastern Europe: 2000-2015. Qual Life Res 2016;25:2693–710. 10.1007/s11136-016-1375-6
    1. Lloyd A, Pickard AS. The EQ-5D and the EuroQol group. Value Health 2019;22:21–2. 10.1016/j.jval.2018.12.002
    1. Koncz B, Darvasi E, Erdősi D, et al. . Lifestyle, prevention and risk of acute pancreatitis (lifespan): protocol of a multicentre and multinational observational case-control study. BMJ Open 2020;10:e029660. 10.1136/bmjopen-2019-029660
    1. Sahin-Tóth M, Hegyi P. Smoking and drinking synergize in pancreatitis: multiple hits on multiple targets. Gastroenterology 2017;153:1479–81. 10.1053/j.gastro.2017.10.031

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