page1of4

Research Proposal
  1. Trial Synopsis

Coordinating
investigator / Simon Hein, M.D.
Department of Urology, University Medical Centre Freiburg
Hugstetter Str. 55, D-79106 Freiburg, Germany
Tel.:+49/761/270-28910
Fax: +49/761/270-28780
Email:
Title of trial / Clinical Significance of Residual Fragments in 2015: Impact, Detection and How to Avoid Them
Objective / Review of the literature concerning outcome parameters relevant to patients with persisting residual fragments afteractive stone treatment and techniques to detect and avoid them
Inclusion and exclusion criteria / Inclusion criteria:
Clinical studies, including systematic reviews (SR), RCTs, cohort studies, case-control studies, case series, EAU and AUA guidelines on urolithiasis
Exclusion criteria:
Case reports, epidemiological studies, cross-sectional studies, cadaveric studies, animal studies
Outcome(s) / Primary endpoint:
Stone-related clinical events (medical treatment, retreatment)
Secondary endpoint(s):
Sensitivity and specificity of different imaging modes
Radiation exposure of imaging modes
Stone free rate of SWL and endourology (URS/ PNL)
Complications of SWL and endourology
Frequency of ancillary procedures in SWL and endourology
Current and future techniques to avoid residual fragments
Trial type / Cross-sectional, comprehensive review (non-systematic)
Statistical analysis / Descriptive analyses ofprimary and secondary endpoints.
Sample size / Max. 60 references to be included
Trial duration / Time for preparation of the trial (months): 3
Data acquisition (months): 3
Statistical analysis (months): 0
Manuscript drafting (months): 3
  1. The Medical Problem

The treatment of urolithiasis has changed dramatically with minimally invasive techniques gradually replacing open surgery since the beginning of the 1970s. In the era of open surgery, complete stone clearance defined a successful treatment [1]. With the introduction of extracorporeal shock wave lithotripsy (SWL), fragments of targeted stones and subsequent expulsion came into focus [2]. ‘Clinically insignificant residual fragments’ (CIRF) were defined as asymptomatic residual fragments of 4 mm or less after SWL [3]. Indeed, occurrence of residual fragments (RF) is not restricted to SWL of renal stones. RF may as well remain after percutaneous nephrolithotomy (PNL) and (flexible) ureteroscopy (fURS) of the kidney and ureter [1, 4]. However, the impact of residual fragments on subsequent stone associated incidents, reoccurrence and growth, remains a subject of discussion [5]. In this review we address various issues concerning the fate of residual fragments (and the patients carrying them), their detection and current and future techniques to avoid them.

  1. Justification of Design Aspects

3.1Inclusion and exclusion criteria

Inclusion criteria:

Clinical studies including systematic reviews (SR), RCTs, cohort studies, case-control studies, case series, non-systematic reviewsand EAU and AUA guidelines on urolithiasis

Exclusion criteria:

Case reports, epidemiological studies, cross-sectional studies, cadaveric studies,animal studies

Assessment of clinical outcome parameters of clinical trials (best available evidence) to answer identified problems relevant to the patient.

3.2Search Method

Databases:

PubMed®, MEDLINE®, Embase™, Ovid®, Google Scholar™, and the Cochrane Library.

Search term:

Boolean searching will be performed using following terms:

“shock wave lithotripsy”, “ureteroscopy”, “percutaneous nephrolithotomy”, “imaging”, “computed tomography”, “clinically insignificant residual fragments”, “CIRF”, and “residual fragments”.

Terms will be linked by Boolean operators AND and OR.

EAU/AUA guidelines will be assessed concerning recommendations and cited references.

3.3Outcome measures

Results will be evaluated concerning primary and secondary endpoints.

Primary endpoint:

Stone-related clinical events (medical treatment, retreatment)

Secondary endpoint(s):

Sensitivity and specificity of different imaging modes

Radiation exposure of imaging modes

Stone free rate of SWL and endourology (URS/ PNL)

Complications of SWL and endourology

Frequency of ancillary procedures in SWL and endourology

Current and future techniques to avoid residual fragments

3.4Methods against bias

Evaluation and rating of extracted article by 2 independent reviewers (S.H. and M.S.). In cases of divergent ratings, results will be verified by a third independent reviewer (A.M.).

  1. Statistical Analysis

Results will be described using descriptive statistics. No further statistical analysis will be performed.

  1. Trial Management

5.1Key participants

# / Name / Affiliation / Responsibility/Role
1 / Simon Hein, M.D. / Dept. of Urology, University Medical Centre Freiburg / Principal investigator
2 / Arkadisz Miernik, M.D., Ph.D. / Dept. of Urology, University Medical Centre Freiburg / Co-Investigator
3 / Konrad Wilhelm, M.D / Dept. of Urology, University Medical Centre Freiburg / Co-Investigator
4 / Fabian Adams, M.D. / Dept. of Urology, University Medical Centre Freiburg / Co-Investigator
5 / Daniel Schlager, M.D. / Dept. of Urology, University Medical Centre Freiburg / Co-Investigator
6 / Thomas Herrmann, M.D., Ph.D. / Department of Urology and Urooncology, Hanover Medical School (MHH) / Co-Investigator
7 / Jens Rassweiler, M.D., Ph.D., Dr. h.c., Prof. / SLK Kliniken Heilbronn
Department of Urology and Pediatric Urology / Co-Investigator
8 / Martin Schoenthaler, M.D., Ph.D. / Dept. of Urology, University Medical Centre Freiburg / Co-Investigator

5.2Supporting facilities

None.

  1. Financing

Institutional funding (Department of Urology, University Medical Centre Freiburg)

6.1Co-financing of the trial by a company: None

  1. References

1.Altunrende, F., et al., Clinically insignificant residual fragments after percutaneous nephrolithotomy: medium-term follow-up. J Endourol, 2011. 25(6): p. 941-5.

2.Osman, M.M., et al., 5-year-follow-up of patients with clinically insignificant residual fragments after extracorporeal shockwave lithotripsy. Eur Urol, 2005. 47(6): p. 860-4.

3.Rassweiler, J.J., et al., Treatment of renal stones by extracorporeal shockwave lithotripsy: an update. Eur Urol, 2001. 39(2): p. 187-99.

4.Ozgor, F., et al., Clinically insignificant residual fragments after flexible ureterorenoscopy: medium-term follow-up results. Urolithiasis, 2014. 42(6): p. 533-8.

5.Tan, Y.H. and M. Wong, How significant are clinically insignificant residual fragments following lithotripsy? Curr Opin Urol, 2005. 15(2): p. 127-31.