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Protocol for a Randomized Phase II Trial for Mesh Optimization by Autologous Plasma Coating in Prolapse Repair: IDEAL Stage 3

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Mesh-related complications especially after vaginal implantation have raised awareness lately because of severe adverse reactions and legal aspects. About 20% of patients suffer from complications after mesh insertion in the anterior vaginal wall. Autologous plasma coating of meshes prior to implantation has shown potential to improve the biocompatibility of meshes in vivo and in vitro. This innovative approach has been developed according to the IDEAL recommendations for surgical innovations. The method has still to be assessed at stage 3 accordingly.


A protocol is developed for a prospective single-blinded randomized controlled phase II trial for biocompatibility optimization of anterior vaginal meshes for prolapse repair by autologous plasma coating versus non-coated meshes.


The protocol aims at fulfilling the requirements for stage 3 (assessment) according to IDEAL. Eligible for inclusion are women with primary cystocele, requiring a surgical procedure, suitable for randomization, and willing to be randomized. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomization) and will also be reviewed in clinic 12 and 24 months post surgery. Primary endpoint is the assessment of mesh-related complications following the Clavien–Dindo classifications. QoL, sexual function assessment, efficacy, and validation of an already developed long-term register are considered secondary endpoints. To afford a calculated 10% reduction of postoperative complications through plasma-coated meshes vs. non-coated meshes at 1-year follow-up, a total 214 women in each arm will be necessary to achieve 80% power at a significance level of 5%.


The protocol for this randomized clinical trial represents the conditions to assess the surgical innovation of plasma coating of meshes in order to improve the meshes’ biocompatibility at stage 3 according to the IDEAL recommendations.

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  1. McCulloch P, Altman DG, Campbell WB, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet. 2009;374(9695):1105–12. doi:10.1016/S0140-6736(09)61116-8.

    Article  PubMed  Google Scholar 

  2. Ergina PL, Cook JA, Blazeby JM, et al. Challenges in evaluating surgical innovation. Lancet. 2009;374(9695):1097–104. doi:10.1016/S0140-6736(09)61086-2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Barkun JS, Aronson JK, Feldman LS, et al. Evaluation and stages of surgical innovations. Lancet. 2009;374(9695):1089–96.

    Article  PubMed  Google Scholar 

  4. Sedrakyan A, Campbell B, Merino JG, Kuntz R, Hirst A, McCulloch P. IDEAL-D: a rational framework for evaluating and regulating the use of medical devices. BMJ. 2016;353:i2372.

    Article  PubMed  Google Scholar 

  5. Vitale SG, Lagana AS, Gulino FA, Tropea A, Tarda S. Prosthetic surgery versus native tissue repair of cystocele: literature review. Updates Surg. 2016;68(4):325–9. doi:10.1007/s13304-015-0343-y.

    Article  PubMed  Google Scholar 

  6. UPDATE on serious complications associated with transvaginal placement of surgical mesh for pelvic organ prolapse: FDA safety communication hwfgMSAuh. Accessed 1 Jan 2017.

  7. FDA Gastroenterology-Urology Medical Devices Advisory Committee Panel. Reclassification of orogynecologic surgical mesh instrumentation. Accessed 1 Jan 2017.

  8. Junge K, Rosch R, Klinge U, et al. Titanium coating of a polypropylene mesh for hernia repair: effect on biocompatibilty. Hernia. 2005;9(2):115–9.

    Article  CAS  PubMed  Google Scholar 

  9. Lukasiewicz A, Skopinska-Wisniewska J, Marszalek A, Molski S, Drewa T. Collagen/Polypropylene composite mesh biocompatibility in abdominal wall reconstruction. Plast Reconstr Surg. 2013;131(5):731e–40e. doi:10.1097/PRS.0b013e3182865d2c.

    Article  CAS  PubMed  Google Scholar 

  10. Sedrakyan A. Metal-on-metal failures–in science, regulation, and policy. Lancet. 2012;379(9822):1174–6. doi:10.1016/S0140-6736(12)60372-9.

    Article  PubMed  Google Scholar 

  11. Chatterjee S, Herrmann HC, Wilensky RL, et al. Safety and procedural success of left atrial appendage exclusion with the lariat device: a systematic review of published reports and analytic Review of the FDA MAUDE Database. JAMA Intern Med. 2015;175(7):1104–9.

    Article  PubMed  Google Scholar 

  12. Kramer DB, Xu S, Kesselheim AS. How does medical device regulation perform in the United States and the European Union? A systematic review. PLoS Med. 2012;9(7):e1001276.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Smith AJ, Dieppe P, Vernon K, Porter M, Blom AW, National Joint Registry of E, et al. Failure rates of stemmed metal-on-metal hip replacements: analysis of data from the National Joint Registry of England and Wales. Lancet. 2012;379(9822):1199–204.

    Article  PubMed  Google Scholar 

  14. Lilford RJ, Braunholtz DA, Greenhalgh R, Edwards SJ. Trials and fast changing technologies: the case for tracker studies. BMJ. 2000;320(7226):43–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gerullis H, Georgas E, Eimer C, et al. Evaluation of biocompatibility of alloplastic materials: development of a tissue culture in vitro test system. Surg Technol Int. 2011;21:21–7.

    PubMed  Google Scholar 

  16. Gerullis H, Klosterhalfen B, Boros M, et al. IDEAL in meshes for prolapse, urinary incontinence, and hernia repair. Surg Innov. 2013;20(5):502–8.

    Article  PubMed  Google Scholar 

  17. Gerullis H, Georgas E, Eimer C, et al. Coating with autologous plasma improves biocompatibility of mesh grafts in vitro: development stage of a surgical innovation. Biomed Res Int. 2013;2013:536814.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gerullis H, Georgas E, Boros M, et al. Inflammatory reaction as determinant of foreign body reaction is an early and susceptible event after mesh implantation. Biomed Res Int. 2014;2014:510807.

    Article  PubMed  PubMed Central  Google Scholar 

  19. McCulloch P. The IDEAL recommendations and urological innovation. World J Urol. 2011;29(3):331–6.

    Article  PubMed  Google Scholar 

  20. Gerullis H, Barski D, Ecke TH, et al. Autologous plasma coating improves the biocompatibility of mesh implants. On the IDEAL way from bench to bedside. Int J Surg. 2016; 36(Suppl 2):S142. doi:10.1016/j.ijsu.2016.11.050.

    Article  Google Scholar 

  21. Barski D, Gerullis H, Georgas E, et al. Coating of mesh grafts for prolapse and urinary incontinence repair with autologous plasma: exploration stage of a surgical innovation. Biomed Res Int. 2014;2014:296498. doi:10.1155/2014/296498.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Barski D, Gerullis H, Ecke TH, et al. In: Register of urogynecological implants: the development of an online platform for registration and outcome measurement according to the IDEAL long-term stage of surgical innovation. Int J Surg 2016;36(Suppl 2):S141–2. doi:10.1016/j.ijsu.2016.11.048.

    Article  Google Scholar 

  23. Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol. 1997;89(4):501–6.

    Article  CAS  PubMed  Google Scholar 

  25. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Rogers RG, Rockwood TH, Constantine ML, et al. A new measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Int Urogynecol J. 2013;24(7):1091–103.

    Article  CAS  PubMed  Google Scholar 

  27. Trutnovsky G, Nagele E, Ulrich D, et al. German translation and validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA revised (PISQ-IR). Int Urogynecol J. 2016;27(8):1235–44.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Barski D, Otto T, Gerullis H. Systematic review and classification of complications after anterior, posterior, apical, and total vaginal mesh implantation for prolapse repair. Surg Technol Int. 2014;XXIV:217–24.

    Google Scholar 

  29. Haylen BT, Freeman RM, Swift SE, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint terminology and classification of the complications related directly to the insertion of prostheses (meshes, implants, tapes) and grafts in female pelvic floor surgery. Neurourol Urodyn. 2011;30(1):2–12.

    Article  PubMed  Google Scholar 

  30. Lenz F, Stammer H, Brocker K, Rak M, Scherg H, Sohn C. Validation of a German version of the P-QOL Questionnaire. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20(6):641–9.

    Article  CAS  PubMed  Google Scholar 

  31. Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol. 1996;175(1):10–7.

    Article  CAS  PubMed  Google Scholar 

  32. Maher C, Feiner B, Baessler K, Christmann-Schmid C, Haya N, Marjoribanks J. Transvaginal mesh or grafts compared with native tissue repair for vaginal prolapse. Cochrane Database Syst Rev. 2016;2:CD012079.

    PubMed  Google Scholar 

  33. Agha R, Fowler AJ, Limb C, et al. The first 500 registrations to the Research Registry®: advancing registration of under-registered study types. Front Surg. 2016;3:50.

    Article  PubMed  PubMed Central  Google Scholar 

  34. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4.

    Article  Google Scholar 

  35. Chapman SJ, Shelton B, Mahmood H, Fitzgerald JE, Harrison EM, Bhangu A. Discontinuation and non-publication of surgical randomised controlled trials: observational study. BMJ. 2014;349:g6870.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Vitale SG, Caruso S, Rapisarda AM, et al. Biocompatible porcine dermis graft to treat severe cystocele: impact on quality of life and sexuality. Arch Gynecol Obstet. 2016;293(1):125–31.

    Article  PubMed  Google Scholar 

  37. Ware JE Jr, Kosinski M, Gandek B, et al. The factor structure of the SF-36 health survey in 10 countries: results from the IQOLA Project. international quality of life assessment. J Clin Epidemiol. 1998;51(11):1159–65.

    Article  PubMed  Google Scholar 

  38. de Tayrac R, Alves A, Therin M. Collagen-coated vs noncoated low-weight polypropylene meshes in a sheep model for vaginal surgery. A pilot study. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(5):513–20.

    Article  PubMed  Google Scholar 

  39. Lo TS, Tan YL, Khanuengkitkong S, Dass AK, Cortes EF, Wu PY. Assessment of collagen-coated anterior mesh through morphology and clinical outcomes in pelvic reconstructive surgery for pelvic organ prolapse. J Minim Invasive Gynecol. 2014;21(5):753–61.

    Article  PubMed  Google Scholar 

  40. Feola A, Endo M, Urbankova I, et al. Host reaction to vaginally inserted collagen containing polypropylene implants in sheep. Am J Obstet Gynecol. 2015;212(4):474 (e1–8).

    Article  PubMed  Google Scholar 

  41. Darzi S, Urbankova I, Su K, et al. Tissue response to collagen containing polypropylene meshes in an ovine vaginal repair model. Acta Biomater. 2016;39:114–23.

    Article  CAS  PubMed  Google Scholar 

  42. Cervigni M, Natale F, La Penna C, Saltari M, Padoa A, Agostini M. Collagen-coated polypropylene mesh in vaginal prolapse surgery: an observational study. Eur J Obstet Gynecol Reprod Biol. 2011;156(2):223–7.

    Article  CAS  PubMed  Google Scholar 

  43. Lo TS, Cortes EF, Wu PY, Tan YL, Al-Kharabsheh A, Pue LB. Assessment of collagen versus non collagen coated anterior vaginal mesh in pelvic reconstructive surgery: prospective study. Eur J Obstet Gynecol Reprod Biol. 2016;198:138–44.

    Article  CAS  PubMed  Google Scholar 

  44. Siniscalchi RT, Melo M, Palma PC, Dal Fabbro IM, Vidal Bde C, Riccetto CL. Highly purified collagen coating enhances tissue adherence and integration properties of monofilament polypropylene meshes. Int Urogynecol J. 2013;24(10):1747–54.

    Article  PubMed  Google Scholar 

  45. Cornwell KG, Zhang F, Lineaweaver W. Bovine fetal collagen reinforcement in a small animal model of hernia with component repair. J Surg Res. 2016;201(2):416–24.

    Article  PubMed  Google Scholar 

  46. Avila OR, Parizzi NG, Souza AP, Botini DS, Alves JY, Almeida SH. Histological response to platelet-rich plasma added to polypropylene mesh implemented in rabbits. Int Braz J Urol. 2016;42(5):993–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Liang R, Knight K, Barone W, et al. Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque. Am J Obstet Gynecol. 2017;216(2):153e1.

    Article  Google Scholar 

  48. Ergina PL, Barkun JS, McCulloch P, Cook JA, Altman DG, IDEAL Group. IDEAL framework for surgical innovation 2: observational studies in the exploration and assessment stages. BMJ. 2013;346:f3011.

    Article  PubMed  PubMed Central  Google Scholar 

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No funding or sponsorship was received for this study or publication of this article.

All authors read and approved the final manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Holger Gerullis and Dimitri Barski contributed equally to this manuscript.


Holger Gerullis, Dimitri Barski, Evangelos Georgas, Mihaly Borós, Albert Ramon, Thorsten H. Ecke, Silvia Selinski, Dörte Luedders, Mario W. Kramer, Alexander Winter, Friedhelm Wawroschek, and Thomas Otto have nothing to disclose.

Compliance with Ethics Guidelines

This trial will be performed according to the Declaration of Helsinki. The protocol will be approved by the regional ethical commissions of the participating centers and possible additional centers. The study will only start once those institutions have given their positive vote. This article does not contain any new studies with human or animal subjects performed by any of the authors.

Data Availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Holger Gerullis.

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Gerullis, H., Barski, D., Georgas, E. et al. Protocol for a Randomized Phase II Trial for Mesh Optimization by Autologous Plasma Coating in Prolapse Repair: IDEAL Stage 3. Adv Ther 34, 995–1006 (2017).

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