Laser Lithotripsy During Ureteroscopy - Holmium vs Thulium: A Clinical Prospective Randomized Trial of Effectiveness and Safety
Phase: NA
Conditions: Urolithiasis
Sponsor: Haukeland University Hospital

Protocol: 
“Laser lithotripsy during ureteroscopy - Holmium vs Thulium. 
A clinical prospective randomized trial of effectiveness and safety.” 
 
 
Authors: 
Ulvik Ø, MD PhD, Assoc. Professor 1,2 
Gjengstø P, MD PhD 1 
Beisland C, MD PhD, Professor 1,2 
 
Affiliations: 
1 Helse Bergen HF, Department of Urology, Haukeland University Hospital, Bergen, Norway 
2 Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway 
 
The authors’ contributions to the study: 
Ø Ulvik is the project manager and is responsible for the overall progress of the study. He 
will write the study protocol, making the data registration forms, patient information and 
consent forms, apply for approval by The National Committees for Research Ethics in 
Norway and The Data Protection Authorities at Haukeland University Hospital (HUH). In 
addition, Ulvik will apply for registration in the clinical research database for randomized 
trials, ClinicalTrials.gov. Ulvik will also be doing the ureteroscopies and follow-up in the study 
patients, sampling data and do the statistical analyses, and write the draft of the manuscript. 
P Gjengstø will do the ureteroscopies, follow-up, sampling of data and contribute to the 
design and content of the manuscript in addition to critical review of the final version. C 
Beisland will contribute to the design and content of the manuscript in addition to critical 
review of the final version. In addition, he will contribute to the data analyses. 
 
 
 

Background: 
Until now, laser lithotripsy during ureteroscopy (URS) has been performed using Holmium: 
yttrium-aluminum-garnet laser. Recently, a new Thulium laser has been introduced. The 
pulsed infrared light emitted by the Thulium laser has a wavelength of 1940 nm which is 
close to the water absorption peak, and the energy delivered by the Thulium laser is 
therefore highly absorbed by water. High water absorption corresponds to low threshold for 
tissue ablation and stone lithotripsy 1. The Thulium laser is therefore expected to be very 
efficient at disintegrating stones. Previous studies have predicted Thulium laser lithotripsy to 
be up to four times faster than Holmium laser lithotripsy using the same energy settings 2. In 
theory, as the threshold for tissue ablation is low, ureteral lesions caused by unintentional 
laser firing at the mucosa may result in less bleeding than with holmium lasers as bleeders 
are instantly coagulated. In addition, the Thulium laser has the advantage of having smaller 
laser fibers enabling better irrigation during URS.  
As the first hospital in Europe, HUH got access to the new Olympus Soltive Premium 
SuperPulsed Thulium Laser System in June 18th 2020. To date, approximately 30 procedures 
have been performed using this laser at our hospital, and the preliminary results seem 
promising.  
The laser has been shown to be a highly efficient tool in the treatment of both ureteral and 
renal stones even at very low energies. Stone burden up to 3.2 cm has been effectively 
cleared. Our impression is that the laser produces significantly smaller fragments and finer 
dust-particles compared to the Holmium laser in shorter time. Fragmenting at a setting of 
0.6 - 0.8 J at 30 Hz (18 - 24 W) produces dust and disintegrates stones faster than dusting at 
0,1 - 0,2 J at 200 - 240 Hz (20 - 48 W), even though the latter setting results in finer dust. 
Complete disintegration of a 1 cm stone at 0,6 J at 30 Hz has been achieved in less than 20 
minutes.  
A remarkable characteristic noted when breaking ureteral stones at low energy, is the 
absence of retropulsion.  
No significant intraoperative complications have been registered so far. However, in a few 
cases small superficial mucosal laser lesions were noted. No bleeding impairing endoscopic 
vision has been registered, and adequate vision was maintained in all without the use of 
irrigation pumps. Insertion of a JJ-stent post endoscopically also seems to be required in a 
few cases only. 

Although the preliminary results of the new Thulium laser look promising, there are no 
clinical randomized trials comparing it to the Holmium laser, which is the current standard 
laser used for URS lithotripsy. 
 
Aims of the study: 
The primary aim of the study is to compare the stone free rate (SFR) following URS 
lithotripsy with Holmium and Thulium lasers. SFRs will be compared both for ureteral stones, 
renal stones and ureteral and renal stones in total.  
Secondary aims are to compare the results of the two lasers in terms of operating times, 
intraoperative complications, postoperative complications and the rate of post endoscopic 
JJ-stenting. 
 
Hypothesis: 
1. The SFR, defined as no residual fragments detected on CT scan 3 months after the 
URS, is higher following lithotripsy with Thulium laser compared to Holmium laser. 
The corresponding H0 is that “there is no difference in SFR following laser lithotripsy 
with the two lasers.” 
2. Operating time following Thulium laser lithotripsy is shorter compared to Holmium 
laser. H0: “There is no difference in the operating time between the two laser 
machines.” 
3. There are less intraoperative complications during Thulium laser lithotripsy 
compared to Holmium laser. H0: “There is no difference in intraoperative 
complications between the two laser machines.” 
4. There are less postoperative complications (infections, readmissions, strictures) 
during Thulium laser lithotripsy compared to Holmium laser. H0: “There is no 
difference in postoperative complications between the two laser machines.” 
5. Fewer patients will need post endoscopic insertion of JJ-stent following Thulium laser 
lithotripsy compared to following Holmium laser lithotripsy. The corresponding H0 is 
that “there is no difference in the frequency of post endoscopic JJ-stent placement 
following laser lithotripsy with the two lasers.” 
 
 

Study design: 
The study is planned performed as a prospective randomized trial. All patients ≥ 18 years 
scheduled to URS lithotripsy at the day surgery unit at HUH are invited to be enrolled in the 
study. After written informed consent, patients are randomized to URS lithotripsy with 
either Holmium laser or Thulium laser.   
 
Randomization: 
The randomization is performed electronically with the same number of patients in each 
group. The results of the randomization are being kept in sealed and consecutively 
numbered envelopes that is opened just before starting the endoscopic procedures in each 
patient. 
 
Patients and data sampling: 
All patients ≥ 18 years scheduled for URS lithotripsy at the day surgery unit at HUH are 
basically eligible for inclusion in this study. Patients with either ureteral stones, renal stones 
or both can be included. The number of patients/procedures needed to be included in the 
study is specified in the Power analysis-section below. 
The following data need to be registered: 
• Preoperative status: 
 
Age, sex, ASA-status, indication for surgery,  
earlier surgery for same stone, stone status, 
acute/planned surgery, prestenting-status, 
infection. 
• Peroperative characteristics: 
Randomization status, primary surgeon,  
antibiotic prophylaxis, operating time, need for 
safety guide wire and access sheath, type of 
endoscope (semi-rigid/flexible), balloon 
dilatation, impacted stone, successful access to 
the stone, laser modality, laser settings, laser 
time and energy used, dusting or fragmentation, 
retrieval of fragments or left for spontaneous 
passage, surgeon’s assessment of post 

endoscopic stone free status, complications, 
placement of JJ-stent. 
• Postoperative status: 
 
Length of hospital stay, immediate complications  
that need urgent treatment, complications after 
discharge requiring readmission, 3-months 
follow-up with CT scan (SFR, stricture rate).  
 
The data will be plotted in a registration form which will be available both electronically and 
on paper. If paper form is used, the data will be registered electronically subsequently and 
the paper-form maculated. Completed registration-forms are transferred to a SPSS database 
for statistical analyses. 
The registration-forms and the database will be stored at Helse-Bergen’s scientific and 
research server in a designated file assigned from the Data Protection Officer. An ID-Key file 
combining personal ID to the registration form will be stored at a designated server for this 
purpose at Helse-Bergen’s research servers. Only the project manager (Øyvind Ulvik) will 
have access to this ID-Key file.  
The registration forms and the ID-Key file will be kept on the server for five years after the 
study has been completed in accordance with the law. After five years the data will be made 
anonymous in terms of deleting the ID-Key file. 
 
Power analysis: 
In an earlier study, we found the 3-months SFR after Holmium laser URS lithotripsy to be 
54.2% using a strict definition of no residual fragments detected on CT scan 3. Although this 
is a strict definition, it leaves no room for personal judgement whether a patient is stone 
free or not. The definition is therefore suitable for this study purpose. 
We expect the Thulium laser to be more efficient in clearing stones than the Holmium laser, 
with a total SFR of around 80% after URS lithotripsy using this laser. 
Comparison of the SFRs between Holmium and Thulium laser will be done using the χ2-test. 
An effect size of 0.3 is considered appropriate assuming the SFRs after Holmium and Thulium 
laser lithotripsy to be 54.2% and 80%, respectively. The α error probability is set to 0.05 and 
the power (1-β error probability) is set to 0.8. Comparison of the SFRs following URS with the 

two lasers with χ2-test is based on a 2 x 2 table, and in this case with only 1 degree of 
freedom (Df).  
Using G*Power, version 3.1.9.4 for power analysis, the total sample size is calculated to be 
88. To compensate for possible non-evaluable patients, a total of 120, i.e. 60 patients in each 
group, are planned to be included in the study.  
 
Statistical analyses: 
Statistical analyses will be performed using IBM SPSS Statistics 25 or higher (IBM, Armonk, 
NY). A p-value < 0.05 will determine statistical significance. 
Continuous variables will be compared using independent-samples t-tests, or in the cases 
were a normal distribution is not met, Mann-Whitney U test. Exact chi-squared test and 
Fisher’s Exact test are used comparing categorical variables. 
 
Ethical considerations, ethical approval and patient consent 
Holmium laser lithotripsy is the gold standard during URS today and is in use worldwide. 
Preliminary results with the new Thulium laser seem promising, however, no randomized 
trials comparing the outcome of the two laser modalities exists. The planned study therefore 
seems to be highly clinically relevant. In addition, the new Thulium laser is approved for use 
during endoscopic lithotripsy and the patients should therefore not be exposed to extra risk 
of harm using this laser. 
Applications for approval by The National Committees for Research Ethics in Norway and 
The Data Protection Authorities at HUH will be sent prior to study start. In addition, the 
study will be registered in the clinical research database for randomized trials, 
ClinicalTrials.gov. 
All patients eligible for inclusion in the study will receive oral and written information. 
Participation in the study is voluntarily, and the patient ca choose to withdraw at any point 
during the study process. Inclusion in the study will only be done after the consent form is 
signed. The patient information and consent form used for this purpose is obtained from The 
National Committees for Research Ethics in Norway’s website 
(https://helseforskning.etikkom.no/frister/malforinformasjonsskriv?p_dim=34672). 
 
 

Laser settings 
The laser settings in the two study groups need to be standardized. The following laser 
settings are suggested as the start-up settings. In the cases of insufficient effect, higher 
energies can be applied but then need to be registered. 
 
 
Ureteral stones: 
0.4 J at 6 Hz (2.4 watts), long pulse 
 
Renal stones:  
0.4 - 0.8 J at 6 - 20 Hz (2.4 - 16 watts) for Holmium and 
0.6 - 0.8 J at 30 Hz (18 - 24 watts) for Thulium. 
 
The initial settings for the Thulium laser when treating renal stones are at a higher watt-level 
compared to the Holmium laser settings, and is therefore expected to be more efficient. 
However, the fact that the Thulium laser is able to deliver more energy needs to be 
considered when comparing the clinical outcome of the two lasers. 
 
Study progress  
The date for completing the data registration form, patient information and consent form, 
and application for approval by The National Committees for Research Ethics in Norway is 
set to 18th of August 2020.  
During August 2020 the application form to The Data Protection Authorities at HUH will be 
sent. Prior to study start the study will also be registered in the clinical research database for 
randomized trials, ClinicalTrials.gov. 
Inclusion of patients and ureteroscopies is expected to start in October 2020, and the 
inclusion is expected to close during March 2021.  
Data analyses and writing a draft is set to spring 2021. Final manuscript ready for submission 
is planned during the summer 2021. 
 
Funding 
No external funding is planned. Hopefully, the project can be completed during regular 
working hours at Haukeland University Hospital and the University of Bergen. 
 
 
 

Conflicts of interest 
Øyvind Ulvik is a consultant for Olympus, who was not involved in the design, collection, 
analyses, interpretation or reporting of the data. The two other authors have nothing to 
disclose. 
 
Publication of data 
The results of the study are planned published as a manuscript in an international urological 
journal (Journal of Endourology, Urology or European Urology). Parts of the results may also 
be presented at international congresses. 
 
 
 
Bergen 05.08.2020 
 
Øyvind Ulvik 
 
 
 
References: 
1. 
Kronenberg P, Traxer O. The laser of the future: reality and expectations about the 
new thulium fiber laser-a systematic review. Transl Androl Urol 2019;8(Suppl 
4):S398-S417. (In eng). DOI: 10.21037/tau.2019.08.01. 
2. 
Traxer O, Keller EX. Thulium fiber laser: the new player for kidney stone treatment? A 
comparison with Holmium:YAG laser. World J Urol 2019 (In eng). DOI: 
10.1007/s00345-019-02654-5. 
3. 
Ulvik Ø, Harneshaug J-R, Gjengstø P. Hvor treffsikker er operatør i sin angivelse av 
stenfrihet etter URS? Høstmøtet 2019.