Protocol for a randomised controlled trial of treatment of asymptomatic candidiasis for the prevention of preterm birth [ACTRN12610000607077]

详细信息    查看全文

• 作者：Christine L Roberts (1) (2)
  Jonathan M Morris (2) (3)
  Kristen R Rickard (1) (3)
  Warwick B Giles (1) (3)
  Judy M Simpson (4)
  George Kotsiou (5)
  Jennifer R Bowen (6)
  
• 刊名：BMC Pregnancy and Childbirth
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：11
• 期：1
• 全文大小：266KB
• 参考文献：1. Saigal S, Doyle LW: An overview of mortality and sequelae of preterm birth from infancy to adulthood. / Lancet 2008, 371 (9608) : 261鈥?69. CrossRef
  2. Iams JD, Romero R, Culhane JF, Goldenberg RL: Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. / Lancet 2008, 371 (9607) : 164鈥?75. CrossRef
  3. Goldenberg RL, Culhane JF, Iams JD, Romero R: Epidemiology and causes of preterm birth. / Lancet 2008, 371 (9606) : 75鈥?4. CrossRef
  4. National Perinatal Statistics Unit: [http://www.preru.unsw.edu.au/PRERUWeb.nsf/page/Perinatal+Statistics] / Australia's Mothers and Babies Reports. / (accessed March 2011)
  5. Petrou S: The economic consequences of preterm birth during the first 10 years of life. / BJOG 2005, 112 (Suppl 1) : 10鈥?5.
  6. Ramachandrappa A, Jain L: Health issues of the late preterm infant. / Pediatr Clin North Am 2009, 56 (3) : 565鈥?77. Table of Contents CrossRef
  7. Goldenberg RL, Hauth JC, Andrews WW: Intrauterine infection and preterm delivery. / N Engl J Med 2000, 342 (20) : 1500鈥?507. CrossRef
  8. Goldenberg RL, Andrews WW, Hauth JC: Choriodecidual infection and preterm birth. / Nutr Rev 2002, 60 (5 Pt 2) : S19鈥?5. CrossRef
  9. Andrews WW, Goldenberg RL, Hauth JC, Cliver SP, Copper R, Conner M: Interconceptional antibiotics to prevent spontaneous preterm birth: a randomized clinical trial. / Am J Obstet Gynecol 2006, 194 (3) : 617鈥?23. CrossRef
  10. Brocklehurst P, Rooney G: Interventions for treating genital chlamydia trachomatis infection in pregnancy. / Cochrane Database Syst Rev 2000, (2) : CD000054.
  11. Gulmezoglu AM: Interventions for treating trichomoniasis in pregnancy. / Cochrane Database Syst Rev 2002, (3) : CD000220.
  12. McDonald HM, Brocklehurst P, Gordon A: Antibiotics for treating bacterial vaginosis in pregnancy. / Cochrane Database Syst Rev 2007, (1) : CD000262.
  13. Raynes-Greenow CH, Roberts CL, Bell JC, Peat B, Gilbert GL: Antibiotics for ureaplasma in the vagina in pregnancy. / Cochrane Database Syst Rev 2004, (1) : CD003767.
  14. Kiss H, Petricevic L, Husslein P: Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery. / BMJ 2004, 329 (7462) : 371. CrossRef
  15. Cotch MF, Hillier SL, Gibbs RS, Eschenbach DA: Epidemiology and outcomes associated with moderate to heavy Candida colonization during pregnancy. Vaginal Infections and Prematurity Study Group. / Am J Obstet Gynecol 1998, 178 (2) : 374鈥?80. CrossRef
  16. Polk BF: Association of Chlamydia trachomatis and Mycoplasma hominis with intrauterine growth retardation and preterm delivery. The John Hopkins Study of Cervicitis and Adverse Pregnancy Outcome. / Am J Epidemiol 1989, 129 (6) : 1247鈥?257.
  17. / Control of communicable diseases manual: an official report of the American Public Health Association 18th edition. Washington, D.C.: American Public Health Association; 2004.
  18. Ferrer J: Vaginal candidosis: epidemiological and etiological factors. / Int J Gynaecol Obstet 2000, 71 (Suppl 1) : S21鈥?7. CrossRef
  19. Holland J, Young ML, Lee O, S CAC: Vulvovaginal carriage of yeasts other than Candida albicans. / Sex Transm Infect 2003, 79 (3) : 249鈥?50. CrossRef
  20. Sobel JD: Vulvovaginal candidosis. / Lancet 2007, 369 (9577) : 1961鈥?971. CrossRef
  21. Sobel JD: Pathogenesis and treatment of recurrent vulvovaginal candidiasis. / Clin Infect Dis 1992, 14 (Suppl 1) : S148鈥?53. CrossRef
  22. Sobel JD: Vaginitis. / N Engl J Med 1997, 337 (26) : 1896鈥?903. CrossRef
  23. Fong IW: The value of treating the sexual partners of women with recurrent vaginal candidiasis with ketoconazole. / Genitourin Med 1992, 68 (3) : 174鈥?76.
  24. Gjerdingen D, Fontaine P, Bixby M, Santilli J, Welsh J: The impact of regular vaginal pH screening on the diagnosis of bacterial vaginosis in pregnancy. / J Fam Pract 2000, 49 (1) : 39鈥?3.
  25. McGregor JA, French JI, Parker R, Draper D, Patterson E, Jones W, Thorsgard K, McFee J: Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation. / Am J Obstet Gynecol 1995, 173 (1) : 157鈥?67. CrossRef
  26. Yim SF, Lyon DJ, Chung TK, Haines CJ: A prospective study of the microbiological environment of the genitourinary tract in Hong Kong Chinese women during pregnancy. / Aust N Z J Obstet Gynaecol 1995, 35 (2) : 178鈥?81. CrossRef
  27. Hay P, Czeizel AE: Asymptomatic trichomonas and candida colonization and pregnancy outcome. / Best Pract Res Clin Obstet Gynaecol 2007, 21 (3) : 403鈥?09. CrossRef
  28. Chaim W, Mazor M, Wiznitzer A: The prevalence and clinical significance of intraamniotic infection with Candida species in women with preterm labor. / Arch Gynecol Obstet 1992, 251 (1) : 9鈥?5. CrossRef
  29. Figueroa R, Garry D, Elimian A, Patel K, Sehgal PB, Tejani N: Evaluation of amniotic fluid cytokines in preterm labor and intact membranes. / J Matern Fetal Neonatal Med 2005, 18 (4) : 241鈥?47. CrossRef
  30. Claveau I, Mostefaoui Y, Rouabhia M: Basement membrane protein and matrix metalloproteinase deregulation in engineered human oral mucosa following infection with Candida albicans. / Matrix Biol 2004, 23 (7) : 477鈥?86. CrossRef
  31. Zaga-Clavellina V, Lopez GG, Estrada-Gutierrez G, Martinez-Flores A, Maida-Claros R, Beltran-Montoya J, Vadillo-Ortega F: Incubation of human chorioamniotic membranes with Candida albicans induces differential synthesis and secretion of interleukin-1beta, interleukin-6, prostaglandin E, and 92 kDa type IV collagenase. / Mycoses 2006, 49 (1) : 6鈥?3. CrossRef
  32. Banhidy F, Acs N, Puho EH, Czeizel AE: Rate of preterm births in pregnant women with common lower genital tract infection: a population-based study based on the clinical practice. / J Matern Fetal Neonatal Med 2009, 22 (5) : 410鈥?18. CrossRef
  33. Czeizel AE, Fladung B, Vargha P: Preterm birth reduction after clotrimazole treatment during pregnancy. / Eur J Obstet Gynecol Reprod Biol 2004, 116 (2) : 157鈥?63. CrossRef
  34. Czeizel AE, Rockenbauer M: A lower rate of preterm birth after clotrimazole therapy during pregnancy. / Paediatr Perinat Epidemiol 1999, 13 (1) : 58鈥?4. CrossRef
  35. Morrison EA, Cushman LF: Prevention of preterm delivery. / N Engl J Med 2007, 357 (19) : 1979鈥?980. CrossRef
  36. Young GL, Jewell D: Topical treatment for vaginal candidiasis (thrush) in pregnancy. / Cochrane Database Syst Rev 2001, (4) : CD000225.
  37. Ruiz-Velasco V, Rosas-Arceo J: Prophylactic clotrimazole treatment to prevent mycoses contamination of the newborn. / Int J Gynaecol Obstet 1978, 16 (1) : 70鈥?1.
  38. Lebherz TB, Ford LC: Candida albicans vaginitis: the problem is diagnosis, the enigma is treatment. / Chemotherapy 1982, 28 (Suppl 1) : 73鈥?9. CrossRef
  39. Pasquale SA, Lawson J, Sargent EC Jr, Newdeck JP: A dose-response study with Monistat cream. / Obstet Gynecol 1979, 53 (2) : 250鈥?53.
  40. MIMS Online: Clotrimazole Prescribing Information
  41. Rosa FW, Baum C, Shaw M: Pregnancy outcomes after first-trimester vaginitis drug therapy. / Obstet Gynecol 1987, 69 (5) : 751鈥?55.
  42. Richter SS, Galask RP, Messer SA, Hollis RJ, Diekema DJ, Pfaller MA: Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. / J Clin Microbiol 2005, 43 (5) : 2155鈥?162. CrossRef
  43. Roberts CL, Rickard KR, Kotsiou G, Morris JM: Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomised controlled trial. / BMC Pregnancy and Childbirth 2011, 11: 18. CrossRef
  44. Hansson L, Hedner T, Dahlof B: Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. / Blood Press 1992, 1 (2) : 113鈥?19. CrossRef
  45. Smith DH, Neutel JM, Lacourciere Y, Kempthorne-Rawson J: Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements. / J Hypertens 2003, 21 (7) : 1291鈥?298. CrossRef
  46. Whitham D, Slicocks P, Whitehouse W, Hodgson S, Sammons H: An example of problems that arise from clinical trials and how to avoid them. / The Pharmaceutical Journal 2009, (283) : 129鈥?30.
  47. Raynes-Greenow CH, Nassar N, Roberts CL: Residential mobility in a cohort of primiparous women during pregnancy and post-partum. / Aust N Z J Public Health 2008, 32 (2) : 131鈥?34. CrossRef
  48. Tabrizi SN, Pirotta MV, Rudland E, Garland SM: Detection of Candida species by PCR in self-collected vaginal swabs of women after taking antibiotics. / Mycoses 2006, 49 (6) : 523鈥?24. CrossRef
  49. Oftadeh S: Genito-urinary colonisation with ureaplasmas - diagnostic aspects. In / Master of Science in Medicine thesis. Sydney: University of Sydney; 2006.
  50. van de Wijgert J, Altini L, Jones H, de Kock A, Young T, Williamson AL, Hoosen A, Coetzee N: Two methods of self-sampling compared to clinician sampling to detect reproductive tract infections in Gugulethu, South Africa. / Sex Transm Dis 2006, 33 (8) : 516鈥?23. CrossRef
  51. Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM: Long-term follow-up of the West of Scotland Coronary Prevention Study. / N Engl J Med 2007, 357 (15) : 1477鈥?486. CrossRef
  52. Ford JB, Roberts CL, Algert CS, Bowen JR, Bajuk B, Henderson-Smart DJ: Using hospital discharge data for determining neonatal morbidity and mortality: a validation study. / BMC Health Serv Res 2007, 7: 188. CrossRef
  53. Lain SJ, Roberts CL, Hadfield RM, Bell JC, Morris JM: How accurate is the reporting of obstetric haemorrhage in hospital discharge data? A validation study. / Aust N Z J Obstet Gynaecol 2008, 48 (5) : 481鈥?84. CrossRef
  54. NSW Health: Validation study NSW Midwives Data Collection 1998. / NSW Public Health Bulletin 2000, (Supp 1) : 97鈥?9.
  55. Roberts CL, Bell JC, Ford JB, Hadfield RM, Algert CS, Morris JM: The accuracy of reporting of the hypertensive disorders of pregnancy in population health data. / Hypertens Pregnancy 2008, 27 (3) : 285鈥?97. CrossRef
  56. Roberts CL, Bell JC, Ford JB, Morris JM: Monitoring the quality of maternity care: how well are labour and delivery events reported in population health data? / Paediatr Perinat Epidemiol 2009, 23 (2) : 144鈥?52. CrossRef
  57. Lain S, Algert C, Nassar N, Bowen JR, Roberts CL: Incidence of severe adverse neonatal outcomes: use of a composite indicator in population data. / Australasian Epidemiologist 2010, 17 (2) : 49鈥?0.
  58. O'Brien PC, Fleming TR: A multiple testing procedure for clinical trials. / Biometrics 1979, 35: 549鈥?56. CrossRef
  59. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/11/19/prepub
  
• 作者单位：Christine L Roberts (1) (2)
  Jonathan M Morris (2) (3)
  Kristen R Rickard (1) (3)
  Warwick B Giles (1) (3)
  Judy M Simpson (4)
  George Kotsiou (5)
  Jennifer R Bowen (6)
  
  1. Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
  2. Department of Obstetrics and Gynaecology, University of Sydney, Sydney, NSW, Australia
  3. Department of Obstetrics and Gynaecology, Royal North Shore Hospital, Sydney, NSW, Australia
  4. School of Public Health, University of Sydney, Sydney, NSW, Australia
  5. Department of Microbiology and Infectious Diseases, Royal North Shore Hospital, Sydney, NSW, Australia
  6. Department of Neonatology, Royal North Shore Hospital, Sydney, NSW, Australia
  

文摘

Background Prevention of preterm birth remains one of the most important challenges in maternity care. We propose a randomised trial with: a simple Candida testing protocol that can be easily incorporated into usual antenatal care; a simple, well accepted, treatment intervention; and assessment of outcomes from validated, routinely-collected, computerised databases. Methods/Design Using a prospective, randomised, open-label, blinded-endpoint (PROBE) study design, we aim to evaluate whether treating women with asymptomatic vaginal candidiasis early in pregnancy is effective in preventing spontaneous preterm birth. Pregnant women presenting for antenatal care <20 weeks gestation with singleton pregnancies are eligible for inclusion. The intervention is a 6-day course of clotrimazole vaginal pessaries (100 mg) and the primary outcome is spontaneous preterm birth <37 weeks gestation. The study protocol draws on the usual antenatal care schedule, has been pilot-tested and the intervention involves only a minor modification of current practice. Women who agree to participate will self-collect a vaginal swab and those who are culture positive for Candida will be randomised (central, telephone) to open-label treatment or usual care (screening result is not revealed, no treatment, routine antenatal care). Outcomes will be obtained from population databases. A sample size of 3,208 women with Candida colonisation (1,604 per arm) is required to detect a 40% reduction in the spontaneous preterm birth rate among women with asymptomatic candidiasis from 5.0% in the control group to 3.0% in women treated with clotrimazole (significance 0.05, power 0.8). Analyses will be by intention to treat. Discussion For our hypothesis, a placebo-controlled trial had major disadvantages: a placebo arm would not represent current clinical practice; knowledge of vaginal colonisation with Candida may change participants' behaviour; and a placebo with an alcohol preservative may have an independent affect on vaginal flora. These disadvantages can be overcome by the PROBE study design. This trial will provide definitive evidence on whether screening for and treating asymptomatic candidiasis in pregnancy significantly reduces the rate of spontaneous preterm birth. If it can be demonstrated that treating asymptomatic candidiasis reduces preterm births this will change current practice and would directly impact the management of every pregnant woman. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12610000607077