Vitamin D to prevent acute lung injury following oesophagectomy (VINDALOO): study protocol for a randomised placebo controlled trial

Trials

David R Thickett³  Fang Gao-Smith³  Gavin D Perkins¹  Derek Alderson³  Olga Tucker³  William D Fraser⁴  Adrian R Martineau²  Mark S Cooper³  Sian Lax³  Rachel C A Dancer³  Dhruv Parekh¹ 

[1] Warwick Medical School Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Warwick, Coventry CV4 7AL, UK;Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, St Dunstan’s Road, London E1 2AB, UK;College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK;Norwich Medical School, University of East Anglia, University Drive, Norwich NR4 7TJ, UK

关键词: Vitamin D;    Oesophagectomy;    One lung ventilation;    Acute lung injury;   

Others  :  1094320
DOI  :  10.1186/1745-6215-14-100

 received in 2012-10-17, accepted in 2013-03-25,  发布年份 2013

【 摘 要 】

Background

Acute lung injury occurs in approximately 25% to 30% of subjects undergoing oesophagectomy. Experimental studies suggest that treatment with vitamin D may prevent the development of acute lung injury by decreasing inflammatory cytokine release, enhancing lung epithelial repair and protecting alveolar capillary barrier function.

Methods/Design

The ‘Vitamin D to prevent lung injury following oesophagectomy trial’ is a multi-centre, randomised, double-blind, placebo-controlled trial. The aim of the trial is to determine in patients undergoing elective transthoracic oesophagectomy, if pre-treatment with a single oral dose of vitamin D₃ (300,000 IU (7.5 mg) cholecalciferol in oily solution administered seven days pre-operatively) compared to placebo affects biomarkers of early acute lung injury and other clinical outcomes. The primary outcome will be change in extravascular lung water index measured by PiCCO® transpulmonary thermodilution catheter at the end of the oesophagectomy. The trial secondary outcomes are clinical markers indicative of lung injury: PaO₂:FiO₂ ratio, oxygenation index; development of acute lung injury to day 28; duration of ventilation and organ failure; survival; safety and tolerability of vitamin D supplementation; plasma indices of endothelial and alveolar epithelial function/injury, plasma inflammatory response and plasma vitamin D status. The study aims to recruit 80 patients from three UK centres.

Discussion

This study will ascertain whether vitamin D replacement alters biomarkers of lung damage following oesophagectomy.

Trial registration

Current Controlled Trials ISRCTN27673620

【 授权许可】

   
2013 Parekh et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Lewandowski K, Lewandowski M: Epidemiology of ARDS. Minerva Anestesiol 2006, 72:473-477.
• [2]Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med 2005, 353:1685-1693.
• [3]Tandon S, Batchelor A, Bullock R, Gascoigne A, Griffin M, Hayes N, Hing J, Shaw I, Warnell I, Baudouin S: Peri-operative risk factors for acute lung injury after elective oesophagectomy. Br J Anaesth 2001, 86:633-638.
• [4]Schilling M, Gassmann N, Sigurdsson G, Regli B, Stoupis C, Furrer M, Signer C, Redaelli C, Büchler M: Role of thromboxane and leukotriene B4 in patients with acute respiratory distress syndrome after oesophagectomy. Br J Anaesth 1998, 80:36-40.
• [5]Schilling M, Eichenberger M, Maurer C, Sigurdsson G, Büchler M: Ketoconazole and pulmonary failure after esophagectomy: a prospective clinical trial. Dis Esophagus 2001, 14:37-40.
• [6]Kuwano H, Sumiyoshi K, Sonoda K, Kitamura K, Tsutsui S, Toh Y, Kitamura M, Sugimachi K: Relationship between preoperative assessment of organ function and postoperative morbidity in patients with oesophageal cancer. Eur J Surg 1998, 164:581-586.
• [7]Ferguson M, Durkin A: Preoperative prediction of the risk of pulmonary complications after esophagectomy for cancer. J Thorac Cardiovasc Surg 2002, 123:661-669.
• [8]Law S, Wong K, Kwok K, Chu K, Wong J: Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg 2004, 240:791-800.
• [9]Baudouin S: Lung injury after thoracotomy. Br J Anaesth 2003, 91:132-142.
• [10]Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000, 342:1334-1349.
• [11]Perkins GD, Park D, Alderson D, Cooke MW, Gao F, Gates S, Lamb SE, Mistry D, Thickett DR: The Beta Agonist Lung Injury TrIal (BALTI) - prevention trial protocol. Trials 2011, 12:79. BioMed Central Full Text
• [12]Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E: Epidemic influenza and vitamin D. Epidemiol Infect 2006, 134:1129-1140.
• [13]Muhe L, Lulseged S, Mason KE, Simoes EA: Case–control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet 1997, 349:1801-1804.
• [14]Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, Timms PM, Venton TR, Bothamley GH, Packe GE, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Mein CA, Bhaw-Rosun L, Nuamah R, Young DB, Drobniewski FA, Griffiths CJ, Martineau AR: Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci U S A 2012, 109:15449-15454.
• [15]Lee P, Eisman JA, Center JR: Vitamin D deficiency in critically ill patients. N Engl J Med 2009, 360:1912-1914.
• [16]Braun A, Chang D, Mahadevappa K, Gibbons FK, Liu Y, Giovannucci E, Christopher KB: Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med 2011, 39:671-677.
• [17]Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB: Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med 2012, 40:63-72.
• [18]Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, Stojakovic T, Schnedl C, Dobnig H: Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care 2011, 15:R104. BioMed Central Full Text
• [19]Hughes DA, Norton R: Vitamin D and respiratory health. Clin Exp Immunol 2009, 158:20-25.
• [20]Zanetti M: Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004, 75:39-48.
• [21]Hansdottir S, Monick MM, Lovan N, Powers L, Gerke A, Hunninghake GW: Vitamin D decreases respiratory syncytial virus induction of NF-kappaB-linked chemokines and cytokines in airway epithelium while maintaining the antiviral state. J Immunol 2010, 184:965-974.
• [22]Shaykhiev R, Beisswenger C, Kandler K, Senske J, Puchner A, Damm T, Behr J, Bals R: Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am J Physiol Lung Cell Mol Physiol 2005, 289:L842-L848.
• [23]Alalwani SM, Sierigk J, Herr C, Pinkenburg O, Gallo R, Vogelmeier C, Bals R: The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. Eur J Immunol 2010, 40:1118-1126.
• [24]Sun J, Kong J, Duan Y, Szeto FL, Liao A, Madara JL, Li YC: Increased NF-kappaB activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 2006, 291:E315-E322.
• [25]Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zugel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A: Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol 2006, 36:361-370.
• [26]Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V: Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 2009, 7:28. BioMed Central Full Text
• [27]Herr C, Branschied M, Vogelmeier C, Bals R: Influence of Vitamin D on the innate immune response in cigarette smoke exposed macrophages. Eur Respir Soc Barcelona meet 2010, A4349.
• [28]Zhou X, Bailey-Bucktrout S, Jeker LT, Bluestone JA: Plasticity of CD4(+) FoxP3(+) T cells. Curr Opin Immunol 2009, 21:281-285.
• [29]Zhou L, Chong MM, Littman DR: Plasticity of CD4+ T cell lineage differentiation. Immunity 2009, 30:646-655.
• [30]Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison M, Walker LS, Lammas DA, Raza K, Sansom DM: 1,25-Dihydroxyvitamin D(3) and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol 2009, 183:5458-5467.
• [31]Schulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. J Pharmacol Pharmacother 2010, 1:100-107.
• [32]Perkins GD, McAuley DF, Thickett DR, Gao F: The beta-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006, 173:281-287.
• [33]Craig TR, Duffy MJ, Shyamsundar M, McDowell C, O'Kane CM, Elborn JS, McAuley DF: A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med 2011, 183:620-626.
• [34]Licker M, Tschopp JM, Robert J, Frey JG, Diaper J, Ellenberger C: Aerosolized salbutamol accelerates the resolution of pulmonary edema after lung resection. Chest 2008, 133:845-852.
• [35]Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky MR, Spragg R, Suter PM: The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling. Intensive Care Med 1998, 24:378-398.
• [36]Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky MR, Spragg R, Suter PM: The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome. Am J Respir Crit Care Med 1998, 157:1332-1347.
• [37]Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL: Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001, 286:1754-1758.