Estimation of the Non-Inferiority of the Laringocel® Videolaryngoscope Compared With the C-MAC D-BLADE (Karl Storz®) for First-Attempt Intubation in Adult Patients Undergoing Elective Surgery
Phase: NA
Conditions: Airway Management, Intubation, Endotracheal
Sponsor: Mario Zamudio

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
1 
 
 
 
This submission includes: 
1. Original protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
2 
 
Estimation of the Non-Inferiority of the Laringocel® Videolaryngoscope 
Compared With the C-MAC D-BLADE (Karl Storz®) for First-Attempt Intubation in 
Adult Patients Undergoing Elective Surgery at Hospital Alma Máter de Antioquia 
(2025–2026). Randomized Non-Inferiority Clinical Trial Protocol. LARINGOCOL 
 
Gabriel Ricardo Muñoz Miranda 
 
 
Thesis protocol submitted in partial fulfillment of the requirements for the degree of 
Master in Clinical Epidemiology 
 
Advisor 
Mario Andrés Zamudio Burbano: Physician and Surgeon, Specialist in Anesthesiology 
and Resuscitation, and Master in Clinical Epidemiology. 
 
 
 
 
 
Universidad de Antioquia 
Faculty of Medicine 
Master in clinical Epidemiology 
Medellín, Antioquia, Colombia 
2025  
 
 
 
 
 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
3 
 
Table of contents  
I. 
Administrative Information .................................................................................... 4 
II. 
Open Science ....................................................................................................... 7 
III. 
Introduction ........................................................................................................... 9 
IV. 
Methods: Patient and Public Involvement, Trial Design ...................................... 17 
V. 
Methods: Participants, Interventions, and Outcomes ......................................... 18 
VI. 
Methods: Allocation of Interventions ................................................................... 29 
VII. 
Methods: Data Collection, Management, and Analysis ....................................... 31 
VIII. 
Methods: Monitoring ........................................................................................... 44 
IX. 
Ethics .................................................................................................................. 44 
X. 
Appendices ......................................................................................................... 49 
XI. 
References ......................................................................................................... 56 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
4 
 
I. 
Administrative Information 
1. Title and Structured Summary  
a. Title: Estimation of the Non-Inferiority of the Laringocel® Videolaryngoscope 
Compared to the C-MAC D-BLADE (Karl Storz®) in First-Attempt Intubation in Adult 
Patients Scheduled for Elective Surgery at Hospital Alma Máter de Antioquia (2025–
2026). Investigator-Initiated Randomized Parallel-Group Non-Inferiority Clinical Trial 
Protocol.  
Short Title: LARINGOCOL  
b. Summary: Dataset from the World Health Organization Trial Registry 
Primary Registry / Trial 
Identifying Number 
x 
Date of Registration in 
Primary Registry 
x 
Secondary 
Identifying 
Numbers 
IN29-2025 
Sources of Monetary or 
Material Support 
Universidad de Antioquia, Hospital Alma Máter de 
Antioquia  
Primary Sponsor 
Universidad de Antioquia  
Secondary Sponsors 
Hospital Alma Máter de Antioquia 
Contact for Public Queries 
Gabriel 
R. 
Muñoz 
Miranda. 
gabrielr.munozm@udea.edu.co 
Contact 
for 
Scientific 
Queries 
Gabriel 
R. 
Muñoz 
Miranda. 
gabrielr.munozm@udea.edu.co 
Public Title 
LARINGOCOL   
Scientific Title 
Estimation of the Non-Inferiority of the Laringocel® 
Videolaryngoscope Compared to the C-MAC D-
BLADE (Karl Storz®) in First-Attempt Intubation in 
Adult Patients Scheduled for Elective Surgery at 
Hospital Alma Máter de Antioquia. 
Countries of Recruitment 
Colombia 
Health 
Condition(s) 
or 
Problem(s) Studied 
First-attempt 
intubation 
success 
rate 
using 
videolaryngoscopy  
Interventions 
Group 1:  
Orotracheal intubation via videolaryngoscopy with the 
Laringocel device. 
Group 2:  
Orotracheal intubation via videolaryngoscopy with the 
C-MAC D-BLADE (Karl Storz®) device 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
5 
 
Key 
Inclusion/Exclusion 
Criteria 
 
Inclusion Criteria: 
• Patients over 18 years of age 
• Patients scheduled for elective surgery under general 
anesthesia 
• Patients requiring orotracheal intubation with a 
single-lumen tube 
 
Exclusion Criteria: 
• Patients with an anticipated difficult airway 
• Patients who decline participation in the study 
Study Type 
Non-inferiority efficacy 
 
Allocation: Randomized, parallel-group, 1:1, 
permuted block design 
 
Masking: Participants and data analyst 
Date of First Enrollment  
Estimated 11/2025 
Target and Final Sample 
Size 
Planned sample: 126 patients per group 
Recruitment Status 
Not yet recruiting 
Primary Outcome 
Proportion of successful first-attempt orotracheal 
intubation 
Key Secondary Outcomes 
i. Estimate whether differences exist between the 
intervention and control in: 
1. Overall intubation success (up to 3 attempts) 
2. Percentage of glottic opening (POGO) 
3. Fremantle score 
4. Intubation time 
5. Operator satisfaction 
6. Situational awareness 
ii. Adverse events in both groups: 
1. Postoperative sore throat (1 hour post-
extubation) 
2. Dental loss 
3. Pharyngeal or oral mucosal injuries 
Ethics Review 
Approved on September 11, 2025 
Trial Completion Date 
Pending 
Summary Results 
Pending 
Individual Participant Data 
(IPD) Sharing Statement: 
Database access will be allowed upon prior request to 
the principal investigator. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
6 
 
Estimated Study Duration: 
12 months 
 
2. Versión del protocolo:  
The development of this protocol has been based on the SPIRIT 2025 Statement 
(Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT 
2010 (Consolidated Standards of Reporting Trials), including the extension for “Non-
Inferiority and Equivalence Trials.” (1,2).  
 
Protocol 
Version 
Date 
Modifications 
Page 
Responsible 
V 1.0 
11/2025 
Initial version  
All  
Principal 
Investigator 
 
3. Roles and Responsibilities: 
a. Gabriel Ricardo Muñoz Miranda1, Mario Andrés Zamudio Burbano2  
 
1 General physician, master’s student in Clinical Epidemiology, Universidad de 
Antioquia. 
Email: gabrielr.munozm@udea.edu.co 
2 Physician and Surgeon, Specialist in Anesthesiology and Resuscitation, and 
master’s in clinical Epidemiology, University of Antioquia. Anesthesiologist at 
Hospital Alma Máter de Antioquia and Professor at the Faculty of Medicine, 
University of Antioquia. Coordinator of the Perioperative Medicine Research Group 
(GRIMPA) 
and 
national 
reference 
for 
EVA 
CLASA. 
Email: mario.zamudio@udea.edu.co 
 
GRM and MZ conceived the study. GRM leads the project, including protocol writing, 
methodological, statistical, and ethical design, overall coordination, and 
dissemination of the proposal. MZ participates as co-investigator and study advisor, 
contributing his expertise in anesthesiology and methodological aspects. He also 
critically reviewed the document and provided corrections and suggestions. 
 
b. Sponsor 
Universidad de Antioquia  
School of Medicine, Master’s Program in Clinical Epidemiology 
Calle 67 No. 53-108, Medellín, Antioquia, Colombia 
Phone: (+57-604) 219 8332 
 
Gabriel R. Muñoz Miranda 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
7 
 
Principal Investigator, Master’s Program in Clinical Epidemiology 
School of Medicine, University of Antioquia 
Email: gabriel.munoz@udea.edu.co 
Phone: +57 3187162895 
 
Mario Zamudio 
Co-investigator and Methodological Advisor 
Specialist in Anesthesiology and Master in Clinical Epidemiology 
School of Medicine, University of Antioquia 
Email: mario.zamudio@udea.edu.co 
 
c. Sponsorship role  
Neither the sponsorship by the University of Antioquia nor that of the authors has 
any influence on the study design; data collection, management, analysis, or 
interpretation; report writing; or the decision to submit the manuscript for 
publication. 
 
d. Coordination:  
This trial will not have a clinical trial coordinating committee. Coordination will be 
the responsibility of the principal author. 
 
II.    Open Science 
4. Study Identifier and Trial Registry Name 
This clinical trial will be registered on the ClinicalTrials.gov platform once the protocol 
is approved. 
5. Access to Protocol and Analysis Plan 
The full protocol will be made available in repositories once approved. 
6. Data Sharing 
Individual participant data will be anonymized and securely stored in Redcap. Upon 
study completion and after publication of the main results, the following will be 
available for a period of 5 years after trial completion: a dataset, the data dictionary, 
and the statistical code used for analyses. These may be shared with other 
researchers upon formal request. External investigators must agree to use the data 
exclusively for research purposes.  
7. Funding and Conflicts of Interest 
a. Funding Sources 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
8 
 
The University of Antioquia financially supports the research director’s time. This 
support includes time dedicated to planning, methodological development, protocol 
writing, and statistical analysis.  
Hospital Alma Máter de Antioquia provides institutional and logistical support, 
granting access to facilities, medical devices, and personnel required for study 
implementation. 
No direct or indirect funding has been received from industry. 
 
b. Funding and Provision of Equipment: 
• 
Provision of the Laringocel device and accessories is funded by the authors, 
without contracts or outcome-related clauses with the company TRONICAL S.A.S. 
• 
Provision of the C-MAC D-BLADE and accessories is funded by Hospital Alma 
Máter de Antioquia, which holds the device in its inventory. 
• 
Gifts and travel support from the manufacturer are prohibited during the study. 
 
c. Conflicts of Interest:  
The research team declares no economic, contractual, or intellectual property ties 
with the manufacturer or distributor of the Laringocel videolaryngoscope 
(TRONICAL). None of the investigators receive fees, financial incentives, in-kind 
support, or benefits derived from commercialization of the device. 
To date, no financial or personal relationships exist with manufacturers or distributors 
of the devices under evaluation (employment, consultancies, honoraria, travel, 
patents, stock ownership, royalties, or others). 
The study’s design, conduct, analysis, and publication are independent from the 
equipment supplier; the supplier does NOT participate in recruitment, has no access 
to real-time data, and holds no veto rights over results or manuscripts. The protocol 
and analysis plan are pre-specified and will be publicly registered (ClinicalTrials.gov) 
prior to the first enrollment. 
The participation of TRONICAL S.A.S is limited to providing, at the request of the 
ethics committee, the regulatory and technical documentation required by INVIMA 
and safety evidence for approval, without involvement in protocol design, trial 
conduct, or result analysis. 
This study is developed as part of a master’s thesis to obtain the degree of Master 
in Clinical Epidemiology at the University of Antioquia. 
 
8. Dissemination Policy 
a. Results Communication Plan  
The authors commit to disclosing the study results regardless of the nature of the 
findings, whether favorable, neutral, or unfavorable. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
9 
 
Initially, results will be presented as a requirement to obtain the Master in Clinical 
Epidemiology degree at the University of Antioquia. They will also be shared with 
the Academic Group of Clinical Epidemiology (GRAEPIC) of the same university, 
with the anesthesiology group at Hospital Alma Máter de Antioquia, and with the 
institution’s Research and Innovation department. 
In a second stage, the findings will be presented at national and international 
academic events in anesthesiology. Finally, the study results will be submitted for 
peer review and potential publication in a scientific journal indexed or recognized 
by Colciencias. 
b. Authorship Plan:  
Authorship assignment for publications derived from the study will follow the 
recommendations of the International Committee of Medical Journal Editors 
(ICMJE). 
For this trial, authorship requires meeting all four criteria: 
1. Substantial contribution to the conception or design of the work, or acquisition, 
analysis, or interpretation of project data. 
2. Drafting the work or critically reviewing it for important intellectual content. 
3. Final approval of the version to be published.  
4. Agreement to be accountable for all aspects of the work, ensuring that questions 
related to accuracy or integrity of any part are appropriately investigated and 
resolved. 
No external professional writers will be engaged in manuscript preparation. 
Document preparation will be the direct responsibility of the research team. 
 
c. Public Access to the Protocol:  
To ensure public access, the protocol will be registered in ClinicalTrials.gov and its 
complete version will be published in a protocol repository such as protocols.io. If 
necessary, it will be made publicly available through publication in an indexed journal 
or 
as 
supplementary 
material 
in 
the 
scientific 
article. 
Regarding the participant dataset and statistical code used for analysis, these will be 
made available upon request to the principal investigator, ensuring protection of 
participant confidentiality. 
 
III. Introduction 
9. Background and Rationale  
a. Problem Statement, Rationale, and Research Question  
In anesthetic practice, orotracheal intubation is generally considered a safe and 
effective procedure (3). However, the Fourth National Audit Project (NAP4) of the 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
10 
 
Royal College of Anaesthetists identified that 42% of adverse events in airway 
management are related to failures in the orotracheal intubation process, making it 
a major cause of morbidity and mortality as well as a frequent reason for medicolegal 
claims against anesthesiologists (4,5). 
These failures are closely linked to difficult airway (DA) scenarios (6), in which most 
adverse events occur during difficult laryngoscopy or tracheal intubation, with a 
combined incidence ranging between 1.8% and 8% (7–9). In this context, 
videolaryngoscopy has emerged as a promising tool due to improved visualization 
and higher success rates (10), although its high cost limits implementation in many 
settings (11). This situation has encouraged the search for more affordable devices, 
such as the Laringocel®, whose performance and safety have not yet been studied, 
highlighting the need for new investigations. 
Difficult laryngoscopy is characterized by the inability to visualize the vocal cords, 
which complicates passage of the endotracheal tube and often requires multiple 
intubation attempts (6). This is significantly associated with increased risk of adverse 
outcomes, such as esophageal intubation (RR 6; 95% CI: 3.7–8.7), severe 
hypoxemia (RR 14; 95% CI: 7.3–24.3), regurgitation (RR 7; 95% CI: 2.8–10), 
bradycardia (RR 4; 95% CI: 1.7–6.7), and cardiac arrest (RR 7; 95% CI: 2.3–9.8). 
Moreover, this situation may culminate in difficult or even failed tracheal intubation 
(7,12). 
These outcomes not only carry significant clinical impact but also increase 
medicolegal claims, often linked to inadequate prediction and poor management of 
difficult airway. Analyses in the United States (2019) and Canada (2020) reported 
that in 59% of cases preoperative evaluation was inadequate, and 65% of errors 
occurred during decision-making (6,13). One major cause of such errors is cognitive 
perseveration bias, manifested in the repetition of the same technique despite failed 
attempts (7,14). For example, Joffe’s study found that, in the face of difficult 
intubation, 67% of physicians persisted in using direct laryngoscopy (15), even 
though subsequent attempts show a failure rate close to 80%. Adopting strategies 
such as changing the operator or using a videolaryngoscope in the second attempt 
can avoid this scenario and raise the success rate to 92% (16).      
he risks associated with DA underscore the importance of accurate prediction; 
however, current clinical tests lack sufficient discriminatory power to anticipate DA, 
representing a major challenge (17,18). Prospective studies indicate that between 
75% and 93% of difficult intubations are unanticipated, increasing the risk of critical 
complications such as the “can’t ventilate, can’t oxygenate” (CVCO) scenario, with 
an incidence of up to 15%  (19–21). Therefore, preparation for unexpected situations 
is essential to achieve first-attempt intubation success, ensuring patient safety 
through the use of the best available tools (7). 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
11 
 
For over a century, direct laryngoscopy has been the standard method for tracheal 
intubation, allowing a direct line of sight between the operator and the glottis (22,23). 
Nevertheless, it fails in up to 8% of cases after three attempts and in 30% on the first 
attempt (7). Given this risk, since 2001 videolaryngoscopy has emerged as a 
promising alternative, as it provides better visualization even in unfavorable anatomy 
and higher first-attempt success rates (4,10). Furthermore, it facilitates teaching and 
enhances situational awareness, supporting real-time shared decision-making (24–
26). 
A recent Cochrane systematic review demonstrated that videolaryngoscopes with 
hyperangulated blades, compared with direct laryngoscopy, reduce the rate of failed 
intubation (RR 0.51; 95% CI: 0.34–0.76) and, in difficult airway cases, further 
decrease this outcome (RR 0.29; 95% CI: 0.17–0.48). They also reduce the rate of 
esophageal intubation (RR 0.39; 95% CI: 0.18–0.81), improve glottic visualization in 
grade 3/4 Cormack-Lehane views (RR 0.15; 95% CI: 0.10–0.24), increase first-
attempt intubation success (RR 1.03; 95% CI: 1.00–1.05), and reduce hypoxemia 
when a Macintosh-type blade is used (RR 0.72; 95% CI: 0.52–0.99). The authors 
concluded that these devices reduce failed intubations, hypoxemia, and improve 
glottic visualization and overall procedural safety (10).   
This positive impact has led to their inclusion in international guidelines such as those 
from the Difficult Airway Society (DAS), the Canadian Airway Focus Group (CAFG), 
and the Project for Universal Management of Airways (PUMA), which recommend 
their routine use as first-line devices (7,27), training all anesthesiologists, and 
ensuring immediate access to this tool (28). These guidelines emphasize maximizing 
success on the first intubation attempt, rather than the second, which is inherently 
more complicated (29). 
Nevertheless, despite the robust evidence supporting videolaryngoscopy and its 
wider availability following the COVID-19 pandemic (30), implementation remains 
limited by economic factors (31). In countries like the United Kingdom, the cost of a 
videolaryngoscope can reach USD 9,273.20, compared with approximately USD 100 
for a Macintosh laryngoscope (32). Moreover, many lower-cost models are 
disposable or use disposable blades, significantly increasing maintenance expenses 
(up to USD 10 per intubation) and raising environmental concerns (33). In high-
volume hospitals, such costs accumulate quickly, hindering widespread adoption 
(11). 
In middle-income countries such as Colombia, adoption of videolaryngoscopes faces 
barriers related to high costs, the need for importation, and lack of accessibility. As 
noted by Arteaga IM —“videolaryngoscopes are unfortunately limited in our setting 
due to cost and maintenance”  (34)—, this situation not only deprives patients of the 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
12 
 
benefits of improved intubation effectiveness but also hinders the training of 
students, residents, and physicians by reducing opportunities to practice in difficult 
airway scenarios (35). 
In response to this need, and following international recommendations, Colombian 
prototypes such as the Laringocel® have been developed—a hyperangulated, 
reusable, non-channeled videolaryngoscope, designed in 2022. Its low cost (~USD 
384) is explained by the use of a borescope transmitting images via Wi-Fi to mobile 
devices (35), eliminating the need for an integrated screen, while offering the 
possibility to store visual material for academic or legal purposes (36); However, no 
studies are currently available comparing its efficacy and safety with established 
devices such as the C-MAC D-BLADE (Karl Storz®), nor assessing the extent to 
which factors such as camera location or dependence on an external device 
influence image quality and usability in surgical settings, as described by other 
investigations (22).  
To address these uncertainties, this project is based on the hypothesis that the 
Laringocel® is non-inferior to the C-MAC D-BLADE (Karl Storz®) in first-attempt 
intubation. 
The results obtained could support the use of the Laringocel® in future cost-
effectiveness studies and facilitate its adoption in clinical settings, offering a more 
economical alternative for videolaryngoscopy. Accordingly, this project poses the 
following research question: 
In patients over 18 years undergoing elective surgery, is the Laringocel® 
videolaryngoscope non-inferior to the C-MAC D-BLADE videolaryngoscope for 
first-attempt intubation? 
b. Choice of Comparator 
There are various types of videolaryngoscopes, classified according to blade 
angulation (hyperangulated or Macintosh-type) and the presence of a channel (with 
or without stylet). Compared with direct laryngoscopy and other videolaryngoscopes, 
these features facilitate intubation in difficult airway (DA) scenarios (10) and the 
guidance of the endotracheal tube (37,38). These devices show a rapid learning 
curve (39), for both inexperienced physicians (26) and those experienced in 
conventional laryngoscopy (21,40)  or other videolaryngoscopes (41). Nonetheless, 
despite their shared principle of indirect visualization, they differ in camera 
placement, illumination, connectivity, and materials, which influence costs, lifespan, 
and the magnitude of benefits (37,42). 
A systematic review and network meta-analysis comparing channeled (Airtraq, 
Airwayscope, and King Vision) and non-channeled (GlideScope, C-MAC, C-MAC D-

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
13 
 
Blade, and McGrath) videolaryngoscopes found significant differences in effect sizes 
for intubation success depending on device and clinical context; in particular, the C-
MAC D-Blade videolaryngoscope stood out for its high success and safety in both 
normal and difficult airways, while other devices showed strengths in aspects such 
as speed, image quality, or intubation time (43).  
These performance discrepancies can largely be attributed to the design of the 
blades and video screens of each device: channeled videolaryngoscopes (Airtraq, 
Airwayscope, King Vision) often have disposable, angulated blades with direct 
screens, facilitating a wide view of the glottis and minimizing maneuvers during 
intubation. In contrast, non-channeled models (GlideScope, C-MAC, C-MAC D-
Blade) require a stylet and have less angulated blades, although they compensate 
with a pronounced distal curvature that reduces cervical movement (22). Given that 
the Storz® C-MAC D-Blade has demonstrated a particularly favorable balance 
between efficacy and safety across different clinical scenarios, and adequately 
represents the design characteristics of non-channeled videolaryngoscopes, it was 
selected as the comparator for the present study. 
c. Evidence for C-MAC D-Blade 
The accumulated clinical evidence consistently supports the performance and safety 
of the C-MAC D-Blade (Karl Storz®) videolaryngoscope. In the general population, 
overall success (up to three attempts) ranges from 81% to 100%, with first-attempt 
success close to 92.7% in patients with difficult airways (22).  In practical terms, ~7 
out of every 100 patients are not intubated on the first attempt with this 
videolaryngoscope; this does not equate to intubation failure, as it is usually resolved 
with subsequent attempts or adjunct maneuvers. Moreover, rates of esophageal 
intubation are very low with videolaryngoscopy; in some series, no events were 
reported, suggesting a favorable safety profile.  
In a randomized trial by Tosh et al., the C-MAC D-Blade showed additional 
advantages over direct laryngoscopy, reducing the incidence of sore throat at 2 hours 
(15.4% vs. 78.5%), eliminating its persistence at 24 hours (0% vs. 67.7%), and 
decreasing hoarseness (0% vs. 13.8%) and cough (4.6% vs. 23.1%) (44). 
Regarding timing, the average time to achieve intubation with this device ranges from 
25 to 32 seconds (43). Although there is heterogeneity by operator, anatomy, and 
stylet strategy, this range positions it as an efficient tool in critical scenarios. Likewise, 
in a randomized non-inferiority trial against GlideScope, the C-MAC D-Blade 
achieved first-attempt success of 507/541 (93.7%; 90.35% CI: 0.917–0.952) (45).  
Finally, a network meta-analysis comparing the C-MAC D-Blade with the Macintosh 
laryngoscope showed in its supplementary material league table that the C-MAC D-

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
14 
 
Blade reduces the odds of failed intubation by 63.5% (OR: 0.365; 95% CI: 0.152–
0.874), decreases the likelihood of difficult intubation by 80.8% (OR: 0.192; 95% CI: 
0.071–0.520), and reduces the chance of difficult laryngoscopy (Cormack–Lehane 
grade ≥3) by 83% (OR: 0.170; 95% CI: 0.074–0.392), with no significant differences 
in mean intubation time (43). Taken together, these effects favor clinical safety and 
efficacy 
Key technical aspects.  
The hyperangulated design facilitates glottic visualization without aligning the 
oropharyngeal–laryngeal–tracheal axes, which is especially useful in difficult airway. 
Since ETTs are optimized for DL, use of a hockey-stick–shaped stylet and a 
progressive stylet withdrawal technique is recommended, in accordance with the 
manufacturer and German airway guidelines (20,36). 
d. Evidence for Laringocel 
Post-marketing observational clinical information on the Laringocel® (TRONICAL®) 
videolaryngoscope was provided by the developing company to the principal 
investigator 
(supplementary 
material 
3). 
In an institutional registry of 534 intubations in the general population, performed by 
both anesthesiologists and non-anesthesiologist physicians, the following outcomes 
were documented:  
- 
First-attempt success rate: 525/534 (98.3%) 
- 
Overall success rate: 532/534 (99.8%) 
- 
Failure rate: 1/534 (0.2%), resolved with fiberoptic bronchoscopy 
With these data, overall success with Laringocel—at two attempts—was 533/534 
procedures (99.8%). Although this is observational evidence, without a control group 
and with possible risk of underreporting, the documented performance suggests a 
high probability of first-attempt success and a very low need for rescue techniques. 
These findings reflect outstanding clinical performance under real-world practice 
conditions, with success proportions comparable to or even exceeding those 
reported for reference videolaryngoscopes, and a minimal frequency of 
complications. Overall, the available evidence supports the potential safety and 
feasibility of Laringocel use in anesthetic practice. 
e. Device comparison 
The Laringocel® and the C-MAC D-Blade (Karl Storz®) are rigid videolaryngoscopes 
that share a pronounced angulation (approximately 45° and 40°, respectively), a 
similar intended use—orotracheal intubation, including difficult airway—and the 
absence of a channel. These shared characteristics allow for a direct comparison 
between both devices in terms of clinical performance and ease of use  (36,46). 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
15 
 
Within the international regulatory framework, the FDA classifies laryngoscopes as 
Class I or II medical devices, subject to technical controls for performance, electrical 
and optical safety, labeling, and validation, without requiring prior clinical studies 
when substantial equivalence with a predicate device exists under the 510(k) 
mechanism (47).  Under this framework, a Class II device such as Laringocel® can 
be evaluated in a randomized controlled clinical trial to measure its performance 
without requiring prior FDA authorization (48).  
In Colombia, Laringocel® holds a valid sanitary registration issued by the National 
Institute for Food and Drug Surveillance (INVIMA) through Resolution No. 
2024036011 dated August 1, 2024, with registration number 2024DM-0029237 and 
a 10-year validity. It was classified as a Class IIa medical device (moderate risk) 
under the Andean Technical Regulation, authorized for manufacture and sale by 
TRONICAL S.A.S. Its intended use in orotracheal intubation, including difficult 
airway, with real-time video transmission to different receiving devices is recognized 
(see supplementary material 2). 
During the evaluation process, INVIMA requested and reviewed the complete 
technical dossier in accordance with current regulations (form ASS-RSA-FM007). 
This included, where applicable, design specifications; electrical, optical, and 
mechanical safety tests; biocompatibility; quality management; labeling and 
instructions for use; as well as software and performance validations. Compliance 
with specific regulatory safety requirements was also mandated: “scientific 
information supporting its safety and performance” (Art. 18, item j, point 15) and the 
“risk analysis issued by the manufacturer” (Art. 18, item j, point 16). Additionally, the 
agency certified the accessory borescope as part of the system, whose medical-
grade components (polycarbonate, aluminum, ceramic, PVC, and encapsulated 
LED) reinforce the device’s technical safety (see supplementary materials 4 and 5). 
f. Expected adverse events 
In 
adults 
undergoing 
orotracheal 
intubation 
with 
a 
non-channeled 
videolaryngoscope, the most relevant adverse events and their expected ranges—
based on literature comparable to the study context—for both devices are:  
a. Esophageal intubation: (≈2.1% with videolaryngoscopy vs 6.6% with direct 
laryngoscopy in the ICU) (49); therefore, we expect ≤1–2% in our trial with trained 
operators in elective surgery. Moreover, several meta-analyses in critically ill 
patients confirm lower esophageal intubation with videolaryngoscopy compared 
with direct laryngoscopy (10,50). Additionally, confirmation by capnography will 
alert to esophageal intubation and will be managed by the attending 
anesthesiologist.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
16 
 
b. Pharyngolaryngeal symptoms: These include postoperative sore throat 
(POST) and cough, most of which are self-limited. A clinical trial with the C-MAC 
D-Blade showed less sore throat at 2 h (15.4% vs 78.5%) and absence at 24 h 
(0% vs 67.7%); it also showed less hoarseness at 24 h (0% vs 13.8%) and less 
cough at 24 h (4.6% vs 23.1%). Based on these data, we expect in both groups 
sore throat ≤15% at 2 h and ≈0–5% at 24 h, hoarseness ≈0% at 24 h, and cough 
≈3–5% at 24 h with videolaryngoscopy (44). 
c. Dental trauma: In the Cochrane systematic review and meta-analysis by Hansel 
et al. (2022), comparing hyperangulated videolaryngoscopy (such as C-MAC D-
Blade) with direct laryngoscopy, the relative risk of dental trauma was 0.51 (95% 
CI: 0.16–1.59; I²=0%), with no statistically significant differences but with a trend 
favoring videolaryngoscopy and very infrequent events (hyperangulated 
videolaryngoscopes: 2/1876 vs 7/1621 with direct laryngoscopy; aggregated data 
from the included trials), so we expect a frequency <1% with both devices (50). 
 
Consequently, the selection of a non-inferiority design is supported by the potential 
benefit of Laringocel®, which may offer a combination of safety and efficacy at an 
affordable cost for the Colombian health system. Thus, the objective is to generate 
evidence supporting the adoption of a more economical device without 
compromising safety or effectiveness in airway management. 
10. Specific Objectives or Hypotheses  
a. Research Hypothesis 
The Laringocel® videolaryngoscope is non-inferior to the C-MAC D-BLADE (Karl 
Storz®) for first-attempt intubation success in patients over 18 years scheduled for 
elective surgery at Hospital Alma Máter de Antioquia. 
 
b. Primary Objective 
To determine whether, in patients over 18 years scheduled for elective surgery, the 
Laringocel® 
videolaryngoscope 
is 
non-inferior 
to 
the 
C-MAC 
D-Blade 
videolaryngoscope for first-attempt intubation. 
 
c. Secondary Objectives  
i. To estimate whether differences exist between the intervention and control in: 
1. Overall intubation success (3 attempts) 
2. Percentage of Glottic Opening (POGO) 
3. Fremantle score 
4. Intubation time 
5. Operator satisfaction 
6. Situational awareness (SAGAT) 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
17 
 
ii. To describe adverse events in both groups: 
1. Postoperative sore throat 
2. Dental loss 
3. Oral mucosal injuries 
d. Trial Estimand 
Attribute 
Definition 
Population 
Adult patients scheduled for elective surgery at Hospital Alma 
Máter de Antioquia who are randomized. 
Intervention 
Experimental group: Laringocel® videolaryngoscope. Control 
group: C-MAC D-BLADE (Karl Storz®). 
Endpoint 
First-attempt intubation success, defined as correct placement 
of the endotracheal tube on the first attempt, confirmed by a 
capnography waveform. 
Summary 
measure 
Difference in proportions of first-attempt intubation success 
between the experimental group and the control group. 
Handling of 
intercurrent 
events 
Device switches: Patients who switch from the assigned 
device (Laringocel or C-MAC) will be excluded from the 
analysis (per-protocol analysis). However, an intention-to-treat 
sensitivity analysis will be performed. 
 
IV. Methods: Patient and Public Involvement, Trial 
Design 
 
11. Patient and Public Involvement  
No direct involvement of patients or the public in the trial design has been planned. 
  
12. Trial Design Description  
This clinical trial is conceived as a non-inferiority study with a parallel-group design 
and 1:1 random allocation using permuted blocks. 
Clinical trials commonly aim to demonstrate superiority. However, when an 
intervention is already well established—as is the case with videolaryngoscopy, 
which achieves first-attempt intubation success rates above 90%—demonstrating a 
significant advantage with a new device is challenging. This is because any 
difference between groups is expected to be small, which would require very large 
sample sizes to detect a statistically significant difference. 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
18 
 
Conversely, a new intervention may demonstrate efficacy and safety similar to the 
current standard, or even a slight decrease in performance, but with substantial 
advantages such as lower cost, greater affordability, and improved availability. In 
such cases, non-inferiority trials allow assessment of whether the new intervention is 
not clinically worse than the accepted standard within a predefined margin, while 
leveraging its additional benefits (51,52).  
 
Therefore, Laringocel® was compared with the C-MAC D-BLADE (Karl Storz®) 
under a non-inferiority design, with the objective of evaluating its performance in 
first-attempt intubation without compromising safety or clinical efficacy, while offering 
the benefits of lower cost, greater affordability, and availability. 
 
V. Methods: Participants, Interventions, and 
Outcomes 
13. Study Setting  
clinical trial will be conducted in Colombia, at Hospital Alma Máter, a high-
complexity university institution in the city of Medellín, Antioquia.  
The institution primarily receives patients from urban areas but also from 
neighboring rural regions and has one hospital-based site and one ambulatory site, 
both included as data collection locations. 
Available infrastructure includes fourteen [14] operating rooms at the main site and 
four [4] at the ambulatory site, equipped with vital signs monitors, capnography, 
videolaryngoscopes [C-MAC D-BLADE, Laringocel], and senior personnel 
specialized in anesthesiology. 
Site selection was based on the availability of candidates for surgery under general 
anesthesia, the presence of operational operating rooms, and the commitment of 
the research team. 
The list of operational sites and operating rooms involved in the study can be 
consulted in Appendix C.  
 
14.  Eligibility 
a. Participants 
Inclusion criteria 
• Patients over 18 years of age 
• Patients scheduled for elective surgery under general anesthesia 
• Patients requiring single-lumen orotracheal intubation 
• Compliance with indication and preoperative fasting 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
19 
 
 
Exclusion criteria 
• Patients with an anticipated difficult airway (more than 2 anatomical risk factors 
for difficult airway) 
• Patient refusal to participate in the study via informed consent 
 
b. Intervention Operators  
Participating physicians must be specialists in Anesthesiology with learning-curve 
experience in both interventions. 
 
15. Intervention and Comparator  
a. SPIRIT items 15a to 15d (53) are described according to the TIDieR checklist 
(54). 
i. Intervention (Laringocel): (See images in Appendix D) 
TIDIeR 
Item   
 
 
BRIEF NAME 
1. 
Intubation with LARINGOCEL 
 
WHY 
2. 
Videolaryngoscopy has been shown to be superior to direct laryngoscopy for first-attempt intubation and 
overall intubation success, with lower rates of hypoxemia, esophageal intubation, and improved glottic view 
(10).  Laringocel is chosen as a relatively affordable, easily accessible videolaryngoscope that can provide 
the benefits of hyperangulated videolaryngoscopes in airway management at lower cost.  
 
WHAT WILL BE USED 
3. 
Materials: Patients will be intubated using the Laringocel videolaryngoscope, a reusable, hyperangulated, 
non-channeled device whose blade is made of polycarbonate. This videolaryngoscope has an integrated 
borescope (camera), illumination guide, the capability to transmit real-time images to mobile devices via Wi-
Fi up to 10 meters, and a 450 mA internal rechargeable battery with 90 minutes of autonomy. 
Images generated by Laringocel will be transmitted through the “Laringocel” mobile application to a Huawei 
MatePad 11 tablet, which will be placed at the patient’s head using an adjustable stand. (A photograph of 
the materials is included in Appendix D.)   
WHAT (PROCEDURES) 
4. 
Procedures: Patients will be under general anesthesia with neuromuscular relaxation, with anesthetic 
induction determined at the discretion of the professional performing the intervention. Neuromuscular 
relaxation will be achieved using depolarizing or non-depolarizing muscle relaxants, according to the 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
20 
 
administrator’s clinical judgment, ensuring at least a dose equivalent to ED95 (effective dose in 95% of 
cases). If succinylcholine is used, the intervention will be performed 45 seconds after drug administration. 
For cisatracurium, a 4-minute wait will be observed, and for vecuronium and rocuronium, 2 minutes before 
proceeding. These intervals are established to ensure adequate muscle relaxation.   
 
WHO PROVIDES 
5. 
The intervention will be performed by anesthesiology specialists who have completed their learning curve, 
assessed by CUSUM (Cumulative Sum). Non-anesthesiologist administrators such as students, interns, or 
anesthesiology residents will be excluded from performing the intervention. 
 
HOW 
6. 
Videolaryngoscopy with Laringocel will be performed in person in the operating room on an individual basis. 
 
WHERE 
7. 
Operating rooms at Hospital Alma Máter, hospital or ambulatory site, Medellín, Antioquia, Colombia. 
 
WHEN AND HOW MUCH 
8. 
The intervention will be carried out once adequate neuromuscular relaxation conditions have been achieved. 
For measurement of the primary outcome, intubation will be performed in a single attempt. If necessary, up 
to three attempts may be performed to assess the overall intubation outcome.  
 
ADAPTATIONS 
9. 
The intervention is not designed as a planned or adaptive procedure and does not contemplate a titration 
approach during its execution. 
 
MODIFICATIONS 
10. 
If the third intubation attempt fails, the intervention may be modified by using C-MAC or direct laryngoscopy, 
at the discretion of the professional in charge of the intervention. If technical failures occur with Laringocel 
(such as connection issues, equipment damage, camera or battery failure), an alternative may be used 
according to the clinical judgment of the intervention administrator. 
 
ADHERENCE 
11. 
To ensure procedural fidelity, the following strategies will be implemented:  
1. All participating anesthesiology specialists will receive a training session on the use of Laringocel, 
the intubation criteria defined in the protocol, and the standardization of the following key concepts: 
intubation attempt, failed intubation, confirmation of intubation. (See definitions in Appendix D.) 
2. Procedure oversight will include subsequent review of the Laringocel intubation recording.   

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
21 
 
 
ii. Comparator (C-MAC D-Blade): 
For more information on Laringocel®, see the official page: https://www.laringocel.com/ 
 
 
TIDIeR 
Item   
 
 
BRIEF NAME 
1. 
Intubation with C-MAC D-BLADE 
 
WHY 
2. 
Videolaryngoscopy with C-MAC D-BLADE has demonstrated, compared with direct laryngoscopy, a higher 
proportion of first-attempt intubation success, reduced probability of failed intubation, reduced likelihood of 
difficult intubation, and reduced risk of difficult laryngoscopy (10,43). C-MAC D-BLADE is chosen as the 
comparator videolaryngoscope due to its documented efficacy and safety and the availability of the device.  
 
WHAT WILL BE USED 
3. 
Materials: Patients will be intubated using the C-MAC D-BLADE videolaryngoscope, a reusable, 
hyperangulated, non-channeled device made of titanium. It is equipped with a high-resolution CMOS camera 
that provides HD-quality images with a resolution of 1280 × 800 pixels. Illumination is provided by two 1 W 
white LEDs. The device is compatible with the universal C-MAC® system, allowing Plug & Play connection 
via a 200 cm C-MAC connection cable. Captured images will be transmitted to an integrated screen on a C-
MAC monitor 8403 ZX Storz® or C-MAC 8104 ZX, which will be positioned at the patient’s head using an 
adjustable stand. The C-MAC® D-BLADE has a working length of 109 mm, a handle width of 28 mm, and a 
distal tip width of 19 mm. (A photograph of the materials is included in Appendix D) (55). 
WHAT (PROCEDURES) 
4. 
Procedures: Patients will be under general anesthesia with neuromuscular relaxation, with anesthetic 
induction determined at the discretion of the professional performing the intervention. Neuromuscular 
relaxation will be achieved using depolarizing or non-depolarizing muscle relaxants, according to the 
administrator’s clinical judgment, ensuring at least a dose equivalent to ED95 (effective dose in 95% of 
cases). If succinylcholine is used, the intervention will be performed 45 seconds after drug administration. 
For cisatracurium, a 4-minute wait will be observed, and for vecuronium and rocuronium, 2 minutes before 
proceeding. These intervals are established to ensure adequate muscle relaxation.   

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
22 
 
 
WHO PROVIDES 
5. 
The intervention will be performed by anesthesiology specialists who have completed their learning curve, 
assessed by CUSUM (Cumulative Sum). Non-anesthesiologist administrators such as students, interns, or 
anesthesiology residents will be excluded from performing the intervention. 
 
HOW 
6. 
Videolaryngoscopy with C-MAC® D-BLADE will be performed in person in the operating room on an 
individual basis. 
 
WHERE 
7. 
Operating rooms at Hospital Alma Máter, hospital or ambulatory site, Medellín, Antioquia, Colombia. 
 
WHEN AND HOW MUCH 
8. 
The intervention will be carried out once adequate neuromuscular relaxation conditions have been achieved. 
For measurement of the primary outcome, intubation will be performed in a single attempt. If necessary, up 
to three attempts may be performed to assess the overall intubation outcome.  
 
 
ADAPTATIONS 
9. 
The intervention with C-MAC® D-BLADE is not designed as a planned or adaptive procedure and does not 
contemplate a titration approach during its execution. 
 
 
MODIFICATIONS 
10. 
If the third attempt fails, the intervention may be modified by using Laringocel or direct laryngoscopy, at the 
discretion of the professional in charge of the intervention. If technical failures occur with C-MAC® D-BLADE 
(such as connection issues, equipment damage, camera or battery failure), an alternative may be used 
according to the clinical judgment of the intervention administrator. 
 
ADHERENCE 
11. 
To ensure procedural fidelity, the following strategies will be implemented:  
1. All participating anesthesiology specialists will receive a training session on the use of Laringocel, 
the intubation criteria defined in the protocol, and the standardization of the following key concepts: 
intubation attempt, failed intubation, confirmation of intubation. (See definitions in Appendix D.) 
2. Procedure oversight will include subsequent review of the C-MAC® D-BLADE intubation recording. 
For 
more 
information 
on 
C-MAC 
D-BLADE 
(Karl 
Storz®), 
see 
the 
official 
page: 
https://www.karlstorz.com/us/en/product-detail-page.htm?productID=1000111723&cat=1000071971 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
23 
 
 
16. Outcomes  
a. Primary 
Between the Laringocel and C-MAC groups, the difference in proportions of first-
attempt intubation success during orotracheal intubation in operating rooms will be 
determined. 
Relevance: First-attempt intubation success is crucial to reduce the risk of 
complications such as hypoxemia, aspiration, and other adverse events associated 
with multiple attempts. A device that enables successful first-attempt intubation 
would improve safety and effectiveness in clinical practice. 
 
b. Secondary: 
i. Overall intubation success proportion: In the Laringocel and C-MAC groups, 
the proportion of intubation success within the first three attempts during 
orotracheal intubation will be measured (each attempt is defined as insertion of 
the videolaryngoscope into the oral cavity). If success occurs on the first attempt, 
no further attempts will be made. 
Relevance: To assess intubation effectiveness with the videolaryngoscopes. 
 
ii. Percentage of Glottic Opening (POGO): In the Laringocel and C-MAC D-Blade 
groups, POGO will be measured during intubation and the mean for each group 
will be calculated; subsequently, the difference in means between groups will be 
analyzed.  
Relevance: Allows quantification of the quality of the laryngeal view obtained 
during intubation. A higher POGO indicates better visualization of the vocal cords.  
 
iii. Fremantle score: In the Laringocel and C-MAC D-Blade groups, the Fremantle 
score—assessing both laryngeal view and ease of intubation—will be recorded. 
Subsequently, the frequencies of these scores will be compared between groups.  
Relevance: Lower values on the ease component indicate a less complicated 
intubation, and the scale allows relating the glottic view to intubation ease. 
 
iv. Intubation time: In the Laringocel and C-MAC groups, the time elapsed from the 
start of the intubation procedure (insertion of the videolaryngoscope into the oral 
cavity) until successful tube placement (confirmation by capnography) will be 
 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
24 
 
measured. The mean intubation time in seconds will be measured using the video 
material, and the mean intubation time in each group will be analyzed.  
Relevance: A shorter intubation time can reduce the risk of hypoxia and other 
adverse events, improving patient safety. 
 
v. Operator satisfaction: In the Laringocel and C-MAC groups, the operator’s 
satisfaction with the device used will be evaluated by four questions addressing 
physical and technical ease of use, overall satisfaction, and willingness to reuse, 
rated on a 1–5 Likert scale. This will be measured after the surgical procedure, 
and the average scores for each group will be analyzed.  
Relevance: For new devices, operator satisfaction is a key factor for adoption 
and sustained use. A videolaryngoscope that meets satisfaction expectations can 
facilitate adherence in daily practice.  
 
vi. Situation Awareness Global Assessment Technique (SAGAT):  
In the Laringocel and C-MAC D-Blade groups, situational awareness will be 
evaluated based on SAGAT.  
An external observer who will view only the videolaryngoscope screen, without 
participating in the intubation, will be queried. The assessment will be performed 
after the procedure using a binary-response form with three questions reflecting 
the three levels of situational awareness (perception, comprehension, 
projection). 
The frequency of responses between the two groups will be compared at each 
level of situational awareness, defining loss of situational awareness as failure in 
at least one level. In addition, the probability of failure will be estimated as a 
function of the device used. 
Relevancia: The fundamental role of non-technical skills and their impact on the 
incidence of adverse events—especially those related to decreased situational 
awareness—is well established (56,57). Real-time visualization of the intubation 
procedure by all members of the surgical team may improve situational 
awareness regarding first-attempt intubation success, even among those not 
directly performing the procedure. This facilitates both timely identification of 
adverse situations and ongoing clinical teaching.  
 
vii. Adverse events 
In the Laringocel and C-MAC D-Blade groups, the proportion of adverse events 
will be described, including postoperative sore throat, dental loss, and evident 
injuries to the pharyngeal or oral mucosa. These events will be assessed by the 
investigator responsible within one hour after extubation, whether in the post-
anesthesia recovery room, intensive care unit, or inpatient wards, as applicable.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
25 
 
Relevance: Documenting injuries in both groups allows determination of adverse 
event incidence and device safety.  
 
17.  Harms 
In accordance with good clinical research practices for clinical trials, all adverse events 
occurring during the study will be collected, assessed, and reported. The evaluated 
intervention (orotracheal intubation via videolaryngoscope) is a routine and safe 
procedure in anesthetic practice; therefore, a significant incidence of serious adverse 
events attributable to the study is not expected. 
Adverse events will be assessed by the responsible investigator immediately after 
patient extubation in the operating room, or as soon as the patient is transferred to the 
post-anesthesia recovery room, intensive care unit, or inpatient ward. This 
assessment will be documented using a structured form and stored on the REDCap 
platform. 
Adverse events will be considered those occurring after the participant’s intervention, 
regardless of their causal relationship with the procedure. However, only those 
adverse events with a direct temporal and clinical relationship to the intubation 
procedure will be considered secondary outcomes of the study—for example, 
postoperative sore throat, dental loss, or injury to the oral or pharyngeal mucosa. 
If an adverse event occurs before the intubation procedure, it will be recorded but not 
as a secondary outcome. 
Any serious and unexpected adverse event occurring during intubation—such as the 
urgent need for a surgical airway or hemodynamic instability—will be documented 
immediately on the corresponding form and reported to the Institutional Ethics 
Committee 
within 
the 
first 
24 
hours, 
following 
Good 
Clinical 
Practice 
recommendations. 
 
18.  Participant Timeline: Enrollment, Interventions, and Assessments 
Patients will be recruited in the inpatient ward or preoperative area, either the day 
before or the same day as surgery. There, inclusion and exclusion criteria will be 
verified to determine eligibility for study participation. Subsequently, the informed 
consent process and signature will take place. 
Once recruited, demographic data collection and baseline assessment will proceed, 
including inspection of the oral cavity to detect preexisting lesions. Intervention 
assignment will be randomized and recorded in opaque envelopes. Allocation will 
remain concealed until the investigator opens the sealed envelope and informs the 
anesthesiologist responsible for intubation. The estimated time between baseline 
assessment and intervention allocation is approximately one hour. 
Approximately 5 minutes will be available for the intervention administrator to prepare 
the necessary elements for videolaryngoscopy (assigned videolaryngoscope, its 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
26 
 
correct functioning and connectivity, a stylet standardized to the device’s shape, and 
the orotracheal tube). 
Patients will be under general anesthesia with neuromuscular relaxation, with 
induction determined at the discretion of the professional in charge. Neuromuscular 
relaxation will be achieved using depolarizing or non-depolarizing muscle relaxants, 
ensuring at least a dose equivalent to ED95. If succinylcholine is used, the intervention 
will be performed 45 seconds after its administration; with cisatracurium, a 4-minute 
wait; and with rocuronium, 2 minutes before proceeding with intubation. Induction and 
neuromuscular relaxation are estimated to take between 2 and 6 minutes. 
The intubation procedure will be carried out with the assigned videolaryngoscope, 
either Laringocel or C-MAC D-Blade, recording the video material for subsequent 
evaluation of primary and secondary outcomes. 
The primary outcome will be first-attempt intubation success. Tube placement will be 
confirmed by end-tidal capnography and will be recorded with a mobile device. 
Surgery will then proceed, with duration varying according to the surgical schedule. 
At the end of the intervention, patients will be transferred to the recovery room. One 
hour after extubation, possible adverse events—such as sore throat, oral mucosal 
injuries, and dental loss—will be assessed. In cases where patients are not extubated 
at the end of surgery, evaluation of these outcomes will be performed at a later stage, 
either in the ICU or at a scheduled assessment. 
The evaluation of intubation videos and outcome adjudication will be carried out by 
another investigator, who will record the Fremantle score, POGO, intubation time, and 
first-attempt intubation success. This analysis will not necessarily be immediate, 
allowing it to be performed within the first 24–48 hours after the intervention, at which 
point the intervention will be closed. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
27 
 
Table 2. Participant schedule: enrollment, interventions, and assessments; POGO (Percentage 
of Glottic Opening) 
 
19.  Sample Size  
The sample size calculation was based on the non-inferiority hypothesis for the 
Laringocel videolaryngoscope, considering first-attempt intubation success as the 
primary outcome.  
 
It is estimated that the first-attempt intubation success rate with the C-MAC D-Blade 
will be 93%, taking as reference the randomized clinical trial by Aziz et al., in which 
a first-attempt success rate of 93.7% was reported (90.35% CI: 91.7%–95.7%)  (45).  
To preserve assay sensitivity, a non-inferiority margin (Δ) of 8 percentage points was 
established, corresponding to the absolute difference between the first-attempt 
success rate with the C-MAC D-Blade (93.7%) (45) and the success rate identified 
for direct laryngoscopy in the Cochrane systematic review (85.4%) (0.083; 90.35% 
CI: 0.056–0.107) (10). 
The sample size was estimated using the formula for non-inferiority trials with 
dichotomous outcomes  (52,58). 
Study Period 
 
Moment 
Recruitment 
Allocation 
Post-allocation 
Close 
−𝑡1 
𝑡0 
𝑡1 𝑡2 𝑡3 𝑡4 𝑡5 𝑡6 𝑡7 𝑡8 
𝑡𝑥 
Recruitment 
 
 
 
 
Eligibility screening 
𝜒 
 
 
 
Baseline assessment 
𝜒 
 
 
 
Informed consent 
𝜒 
 
 
 
Allocation                       
𝜒 
 
 
Interventions 
 
 
 
 
 
 
 
 
 
 
 
Laringocel 
 
 
 
 
 
 
 
 
 
 
 
C-MAC D-BLADE 
 
 
 
 
 
 
 
 
 
 
 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
First-attempt success 
 
 
 
 
 
𝜒  
 
 
 
 
Overall success 
 
 
 
 
 
𝜒  
 
 
 
 
Fremantle score – 
POGO 
 
 
 
 
𝜒  
 
 
 
𝜒  
Intubation time 
 
 
 
 
 
 
 
 
 
𝜒  
Operator satisfaction 
 
 
 
 
 
 
 
𝜒  
 
 
Adverse events 
 
 
 
 
 
 
 
𝜒  
 
 
Delayed adverse 
events 
 
 
 
 
 
 
 
 
𝜒  
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
28 
 
2𝑁= 4𝑝(1 −𝑝)(𝑍𝛼+ 𝑍𝛽)
𝛿2
  (1) 
 
 
Where: 
• 
𝑝= 0.93: Expected success proportion 
• 
𝛿= 0.08: Non-inferiority margin. 
• 
𝑍𝛼= 1.645: One-sided 5% significance level. 
• 
𝑍𝛽= 0.84: 80% power. 
 
The calculation was implemented in the R statistical software (v4.4.3, R Core Team 
2025) and validated using the Sealed Envelope Ltd. 2012 Power calculator for 
binary outcome non-inferiority trial. A sample size of 126 patients per group was 
obtained, 
for 
a 
total 
of 
252 
patients 
overall. 
No multiplicity correction was applied to the sample size calculation because there 
will be only one confirmatory outcome; furthermore, due to the brief duration of the 
intervention and data collection, losses are not expected; therefore, no correction 
for drop-out was applied.  
20. Recruitment Strategy  
Participant recruitment will be carried out at the two sites of Hospital Alma Máter 
(hospital-based and ambulatory), selected based on the availability of patients, 
operating rooms, and anesthesiologists. 
The study investigators (trained to identify predictors of difficult airway) will evaluate 
patients in the surgical preparation area or earlier, according to the same-day or next-
day surgical schedules, as appropriate. Patients scheduled for surgery under general 
anesthesia will be identified. Once selected, the medical record will be reviewed and 
the preoperative physical examination performed to confirm eligibility criteria. 
The recruitment period is estimated at eight to twelve months, subject to the flow of 
scheduled patients and the availability of the research team. Currently, approximately 
thirty surgical procedures are performed per day, Monday through Saturday, at the 
hospital-based sites, of which an estimated 20% require orotracheal intubation, 
representing a potentially eligible group for the study and an opportunity to maintain 
steady recruitment. 
To minimize losses to follow-up for postoperative secondary outcomes, a detailed 
record of participants will be maintained. In cases where patients are not extubated 
immediately, the evaluation will be performed in the intensive care unit (ICU) or 
inpatient ward once extubation has taken place. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
29 
 
Participation in the study will not entail additional costs for patients nor modifications 
to their usual anesthetic management. In addition, no financial incentives for 
participants are contemplated. 
 
 
Table 3. Monthly evaluation of recruitment status 
 
VI. Methods: Allocation of Interventions  
Randomization  
21.  Method of Generating the Allocation Sequence  
a. Who generates the sequence and method  
The randomization sequence will be generated by an independent investigator not 
involved in recruitment, patient intervention, or data collection. The sequence will be 
generated using the R statistical software (v4.4.3, R Core Team 2025) and its 
graphical interface RStudio.   
 
b. Type of randomization  
Participants will be randomly assigned to the Laringocel and C-MAC D-Blade groups 
in a 1:1 ratio. Permuted blocks (random sizes of 4, 6, or 8 patients) will be used with 
a computer-based random number generator. 
 
22.  Allocation Concealment Mechanism  
Allocation concealment will be ensured through the use of opaque, sealed, 
sequentially numbered envelopes. These envelopes will be kept locked in a safe, 
Recruitment month 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Current enrollments (current) 
  
  
  
  
 
 
 
 
 
 
 
 
Enrollments to date 
  
  
  
  
 
 
 
 
 
 
 
 
Target enrollments to date 
  
  
  
  
 
 
 
 
 
 
 
 
Actual minus projected 
  
  
  
  
 
 
 
 
 
 
 
 
Success proportion 
  
  
  
  
 
 
 
 
 
 
 
 
Final projected enrollment 
  
  
  
  
 
 
 
 
 
 
 
 
Final deficit or surplus 
  
  
  
  
 
 
 
 
 
 
 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
30 
 
with access restricted to authorized investigators only. The same investigator who 
generates the allocation sequence will be responsible for coding and recording the 
allocation list in opaque, sequentially numbered envelopes (e.g., Pac001, Pac002, 
etc.) and will safeguard this information under strict confidentiality. 
23.  Implementation 
Participants will be assessed for inclusion by the investigator in charge of recruitment 
the day before or the same day as surgery, according to the preoperative schedule. 
Once inclusion and exclusion criteria have been verified and informed consent 
obtained, the patient’s data, date, time, and the investigator’s signature will be 
documented 
on 
the 
outside 
of 
the 
corresponding 
envelope. 
Only at that moment will the assigned envelope be opened, the anesthesiologist 
responsible will be informed of the assigned intervention, and the assigned device 
will be provided for preparation. This procedure ensures that neither recruiting 
personnel nor patients know the allocation before enrollment, preventing selection 
bias. 
 
24.  Blinding (Masking) 
a. Who will be blinded 
Dado el diseño del estudio, se implementarán distintas estrategias de cegamiento 
para minimizar sesgos de desempeño, medición y análisis: 
1. Participants 
2. Data analyst 
Outcome assessors for primary and secondary endpoints will be trained adjudicators; 
however, because the capnography waveform video is needed for the primary 
endpoint, 
blinding 
the 
assessors 
to 
the 
intervention 
is 
not 
possible. 
Operators of the intervention (anesthesiologists in this trial) performing the intubation 
cannot be blinded, as the devices have evident physical differences (see images in 
Appendix D). However, performance bias will be mitigated by keeping them blinded to 
the study’s purpose (i.e., whether it is superiority, equivalence, or non-inferiority). 
 
 
b. How masking will be achieved: 
Patients will be blinded to the assigned intervention because orotracheal intubation 
is performed under general anesthesia. However, knowledge of the device is not 
anticipated to impact on the effect size. 
The investigator responsible for statistical analysis will be blinded to the intervention 
groups. This will be implemented by blinded coding in the study database within the 
REDCap® platform, which allows concealing group names and working with neutral 
labels (Group A and Group B).  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
31 
 
 
c. Emergency unblinding:   
Because the study compares two widely known medical devices, approved by 
INVIMA and used in routine patient care (C-MAC and Laringocel), and because the 
intervention is performed under general anesthesia, no clinical circumstances are 
anticipated in which knowledge of group assignment is essential for patient 
management. Additionally, operators are not blinded and know the assigned device 
from the outset. For these reasons, a formal emergency unblinding procedure is not 
contemplated in the protocol. Any adverse situation will be managed according to 
institutional clinical guidelines, regardless of the assigned group. 
VII. Methods: Data Collection, Management, and 
Analysis 
25. Data Collection Methods 
a. Plans for assessment and data collection  
i. Baseline characteristics  
Through physical examination and review of the medical record conducted by 
the recruiting investigator, the following demographic and clinical variables will 
be recorded: age, body mass index (BMI), sex, place of origin, educational level, 
Mallampati classification, dentition status, mouth opening and ability for 
mandibular protrusion, type of surgical procedure, number of previous surgeries, 
patient status, surgical risk, type of surgery, surgery time, and anesthesia time. 
 
ii. Primary outcome Assessment  
The study’s primary endpoint will be first-attempt intubation success, defined as 
successful placement of the orotracheal tube in the trachea without the need for 
a second attempt. For this study, an intubation attempt will be considered 
complete when the videolaryngoscope is inserted into the oral cavity and 
withdrawn after attempting placement of the endotracheal tube. Intubation will be 
considered successful when, after the attempt, correct placement is confirmed 
by continuous capnography tracing, a method with sensitivity and specificity 
close to 100% for verification of endotracheal intubation (59).  
Intubation will be considered successful by capnography if a sustained exhaled 
CO₂ tracing is detected, meeting the following criteria:   
1. The CO₂ level increases during expiration and decreases during 
inspiration. 
2. The capnographic tracing shows consistent or increasing amplitude for at 
least 7 breaths. 
3. The peak CO₂ amplitude is at least 7.5 mmHg above baseline. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
32 
 
4. The capnogram pattern is clinically appropriate, avoiding false readings in 
contexts incompatible with alveolar ventilation. 
An attempt will be considered failed if there is a device switch, manipulation by a 
third party, withdrawal of the videolaryngoscope from the mouth, or absence of 
effective 
capnography. 
Assessment of the primary endpoint will be performed using the video material 
obtained 
during 
intubation 
by 
an 
investigator. 
Data will be stored in the institutional database (REDCap) and will be subject to 
internal audits to minimize data capture errors. 
 
iii. Secondary outcome assessment  
1. Overall intubation percentage  
In this trial, overall intubation success is defined as successful placement of the 
orotracheal tube in the trachea in a maximum of three attempts using the same 
technique, in accordance with usual clinical practice. The same criteria used for 
first-attempt success will be maintained, including confirmation of correct tube 
placement by continuous capnography tracing. 
The outcome will be assessed by the outcome-adjudicating investigator using 
video material, recording the total number of attempts required, the device, and 
any maneuvers used. 
Intubation will be considered failed if there is protocol deviation. 
2. POGO 
After reviewing the intubation video material, the investigator will record in the 
electronic form a number between 0 and 100%, corresponding to the maximum 
Percentage of Glottic Opening. It is defined as the visual estimate of the 
proportion of the vocal cords or glottic opening seen during videolaryngoscopy; 
0% indicates that no vocal cord structures are visualized, and 100% indicates 
complete visualization from the anterior to the posterior commissure of the vocal 
cords (60,61).  Intermediate values correspond to the approximate estimate of 
the visible portion of the vocal cords.  
POGO has shown inter-rater reliability of 0.614 (95% CI, 0.461–0.740) and 
accuracy (75.5%) significantly greater than Cormack–Lehane (p < 0.001) (62). 
 
3. Fremantle score 
After reviewing the intubation video material, the investigator will record the 
Fremantle score (63), which integrates: 
• The best laryngeal view obtained (F = full view of the laryngeal inlet, P = 
partial view of the glottis, N = no laryngeal structures visible). 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
33 
 
• Ease of intubation (1 = easy, tube passes on the first attempt; 2 = modified, 
requires additional attempts or non-predefined maneuvers; 3 = 
unattainable or technique abandoned). 
• The device used for intubation—in this case, C-MAC D or Laringocel. 
The Fremantle score allows relating the glottic view to intubation ease and the 
device used; it shows accuracy of 73.7% and inter-rater reliability of 0.618 (95% 
CI, 0.616–0.622), both superior to Cormack–Lehane (p < 0.001) 
POGO and the Fremantle score are more reliable than the Cormack–Lehane 
classification for documenting the glottic view in videolaryngoscopy (62). 
 
4. Intubation time  
Intubation time with videolaryngoscope is defined as the interval between 
insertion of the blade into the oral cavity and the first positive capnography 
recording. The investigator will time the intubation by viewing the procedure’s 
video material and will record it in the data collection form. 
 
5. Satisfaction 
After the intervention, the anesthesiologist in charge of the videolaryngoscopy will 
rate the device according to the following criteria (64) using a Likert scale: 
- 
Technical ease of use:   
How easy was it to visualize the glottis?  
(1 = easy to 5 = difficult) 
- 
Physical ease of use 
How comfortable was it to handle the device?  
(1 = easy to 5 = difficult) 
- 
Overall satisfaction 
How satisfied were you with the device’s performance? (1 = very satisfied to 
5 = not at all satisfied) 
- 
Willingness to reuse 
Would you use this device again for future intubations?  
(1 = I would like to use it to 5 = I would never use it again) 
6. SAGAT:  
Situational awareness of the external observer will be evaluated using an 
adaptation of SAGAT, focusing on three levels: perception, comprehension, and 
projection (56,65). 
The external observer (medical students, nursing staff, or an anesthesiology 
resident), without taking part in the intubation, will evaluate the situation 
exclusively 
from 
the 
videolaryngoscope 
screen/monitor. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
34 
 
SAGAT assessment will be performed immediately after the procedure and 
recorded on a structured form using dichotomous responses defined for each 
level: 
• Perception  
The observer’s ability to recognize key anatomical structures on the screen 
will be evaluated. The observer will be asked: Do you see the vocal cords? 
YES/NO 
• Comprehension 
The observer’s ability to understand first-attempt intubation success/failure 
will be evaluated. The observer will be asked: Was the patient intubated 
on the first attempt? YES/NO.  
• Projection 
The observer’s ability to anticipate decision-making based on 
comprehension will be evaluated. The observer will be asked: Is any 
additional maneuver needed regarding the previous point? YES/NO. If 
YES, which one? 
 
Data will be stored in the institutional database (REDCap) and will be subject to 
internal audits to minimize data capture errors.  
 
7. Adverse events  
Adverse events (dental loss, sore throat, and mucosal injuries) are events that 
may occur in the usual context of orotracheal intubation, whether with direct 
laryngoscopy or videolaryngoscopy, and will be reported in accordance with good 
clinical trial practices. 
Upon arrival in the recovery room, the designated investigator will inspect the oral 
and pharyngeal cavity to identify evident mucosal injuries, dental loss, or other 
alterations. In addition, the patient will be asked about the presence or absence 
of sore throat. 
In cases where patients are not extubated immediately, follow-up and evaluation 
by the investigator will be ensured once extubation occurs. All findings will be 
recorded on the data collection form.  
 
b. Plans to promote patient retention and complete follow-up 
For this trial, all randomized patients will complete their participation once 
extubation and the evaluation of safety outcomes have been performed. Loss to 
follow-up is not expected due to the short duration of the intervention. 
Investigators will make reasonable efforts to ensure follow-up of each patient 
through extubation and evaluation of safety outcomes. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
35 
 
To minimize participant loss, various follow-up strategies will be implemented. A 
detailed record will be maintained with contact information and key clinical data that 
allow locating participants within the hospital in those patients who are not 
extubated immediately in the operating room. 
Participants have the right to withdraw from the study at any time and for any 
reason. 
 
26.  Data Management 
Study data will be collected through electronic forms and subsequently stored in 
the institutional database (REDCap). 
Data entry will be local and carried out by the investigators responsible for capture. 
Variables will be coded and categorized according to their nature, level of 
measurement, form of relationship, and unit of measurement (see Table 4). 
To ensure security and access control, the cloud database will be accessible only 
to authorized investigators, who must have specific permissions associated with 
their institutional email. 
To promote data quality and accuracy, an internal audit process will be 
implemented, whereby an investigator different from the one who performed the 
initial capture will review the database to identify possible inconsistencies. In 
addition, backups of the cloud database will be created every 72 hours to prevent 
data loss.  
 
27. Statistical Methods  
a. Between-group comparisons  
i. Baseline characteristics 
Clinical and demographic characteristics of participants will be described in Table 5. 
Quantitative variables will be summarized with mean and standard deviation (SD) 
when they follow a normal distribution (assessed using the Shapiro–Wilk test and 
graphical methods), and with median and interquartile range (IQR) when normality 
is not met. Qualitative variables will be reported as absolute frequencies (n) and 
percentages (%). 
No statistical comparisons between groups will be performed for baseline variables, 
in accordance with good reporting practices in randomized clinical trials, since 
random allocation aims to balance characteristics between groups and any observed 
differences are assumed to be due to chance. 
 
Baseline demographic and clinical characteristics of patients 
 
Characteristics 
Laringocel 
(n=) 
C-MAC D-Blade 
(n=) 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
36 
 
Age, years 
 
 
Sex — n (%) 
Female 
Male  
 
x 
x 
 
x 
x 
Weight, kg 
Height, cm 
BMI, kg/m² 
Place of residence, n (%) 
Urban 
Rural 
 
x 
x 
 
x 
x 
 Mallampati classification — n 
(%) 
I 
II 
III 
IV 
 
x 
x 
x 
x 
 
x 
x 
x 
x 
Number of previous surgeries 
x 
x 
Dentition status — n (%) 
Good 
Poor 
Edentulous 
 
x 
x 
x 
 
x 
x 
x 
ASA classification — n (%) 
ASA I 
ASA II 
ASA III 
 
x 
x 
x 
 
x 
x 
x 
Patient status — n (%)  
Outpatient 
Inpatient 
 
x 
x 
 
x 
x 
Surgical risk — n (%) 
Low risk 
Moderate risk 
High risk 
 
x 
x 
x 
 
x 
x 
x 
Surgical specialty/model, n (%) 
General surgery 
Orthopedic 
Urologic 
Gynecologic 
Neurosurgical 
Plastic surgery 
Otorhinolaryngology 
Ophthalmology 
Vascular 
Other 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
General anesthesia technique, n 
(%) 
Balanced — halogenated agents 
Total intravenous anesthesia 
 
x 
x 
 
x 
x 
Surgery time, min 
x 
x 
Anesthesia time, min 
x 
x 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
37 
 
Thyromental distance, cm 
x 
x 
Sternomental distance, cm 
x 
x 
Thyromental height, mm 
x 
x 
Neck circumference, cm 
x 
x 
Inter-incisor distance, cm 
x 
x 
Cervical spine mobility n (%)  
Normal, 
Reduced 
Fixed 
x 
x 
Upper-lip bite test, n (%) 
I 
II 
III 
x 
x 
Table 5. Baseline characteristics of participants. μ: mean; SD: standard deviation; kg: kilograms; 
cm: centimeters; BMI: body mass index; ASA: American Society of Anesthesiology; Me: 
median; IQR: interquartile range. 
 
ii. Primary endpoint 
Difference in proportions at first intubation attempt. 
 
a. Null hypothesis  
𝜋𝐿𝑎𝑟𝑖𝑛𝑔𝑜𝑐𝑒𝑙 − 𝜋𝐶𝑀𝐷 ≤− 𝛿  
 
b. Alternative hypothesis  
𝜋𝐿𝑎𝑟𝑖𝑛𝑔𝑜𝑐𝑒𝑙 − 𝜋𝐶𝑀𝐷 > − 𝛿  
 
To evaluate non-inferiority in the difference in proportions of successful first-attempt 
intubation between Laringocel and C-MAC, the Farrington and Manning test will be 
applied, as it is considered a robust method for non-inferiority trials with binary 
outcomes. The non-inferiority delta is defined (𝛿−0.08), reflecting the maximum 
acceptable difference for Laringocel to be considered non-inferior to C-MAC D-
BLADE 
This approach explicitly incorporates the non-inferiority hypothesis (the tolerance 
that Laringocel may be up to a certain margin Δ non-inferior to the standard) into 
the variance estimation. In this way, equations are solved that adjust the proportions 
assuming the difference stipulated by the non-inferiority margin, and then the test 
statistic and confidence interval are calculated based on that “restricted” variance. 
This procedure reduces the risk of underestimating uncertainty when success 
proportions are very high and provides a more robust framework for concluding 
whether Laringocel is non-inferior to C-MAC (66–68).  
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
38 
 
𝑍𝐹𝑀 = 
(𝑝1
̂ − 𝑝2
̂) − (−∆)  
 √𝑝1 
̃(1 −𝑝1 
̃)
𝑛1
+ 𝑝2 
̃(1 −𝑝2 
̃)
𝑛2
   (2) 
Where: 
• 𝑝1
̂ 𝑎𝑛𝑑  𝑝2
̂ are the observed success proportions in the Laringocel and C-
MAC groups, respectively. 
• −∆ is the non-inferiority margin. 
• 𝑝1 
̃𝑎𝑛𝑑  𝑝2 
̃ are the “restricted” proportions estimated under the null 
hypothesis that 𝑝1 − 𝑝2 = −∆. These are obtained by solving maximum 
likelihood equations that impose this restriction. 
• 𝑛1 𝑎𝑛𝑑 𝑛2 are the sample sizes of each group.  
• The numerator compares the observed difference with the maximum 
tolerable difference (−∆)   
• The denominator represents the variance adjusted to the non-inferiority 
hypothesis. 
 
If the lower limit of the 90% CI is < 0.08, Laringocel will be considered non-inferior 
(see Figure 1). 
 
 
Figure 1. Potential outcomes for the difference in proportions between Laringocel and C-
MAC D-Blade. LL: lower limit of the 90% CI.  
 
Secondary outcomes will be considered exploratory. For these analyses, p-values and 
95% confidence intervals will be reported without adjustment for multiplicity, since they 
do not constitute confirmatory hypotheses.  
For comparison of quantitative variables between the Laringocel and C-MAC D-Blade 
groups, the Student’s t test for independent samples will be used, provided the 
assumptions of normality of the distribution (assessed by the Shapiro–Wilk test) and 
homogeneity of variances (assessed by Levene’s test) are met. If these assumptions 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
39 
 
are not met, the nonparametric Mann–Whitney U test will be employed to compare 
medians between groups. Comparison of qualitative variables between groups will be 
conducted using Pearson’s chi-square test, considering its use valid when at least 
80% of expected cells have a frequency ≥5. If this criterion is not fulfilled, Fisher’s 
exact test will be used. 
Additionally, for the “projection” outcome of the SAGAT instrument, recognizing its 
logical dependence on the “comprehension” dimension, a logistic regression analysis 
will be applied, adjusting for the response at the comprehension level.  
 
Multiplicity 
Primary non-inferiority hypothesis will be evaluated with a one-sided significance 
level of α = 0.10. 
Additionally, a serial gatekeeping procedure will be applied for three confirmatory 
secondary endpoints. Conditional on demonstrating non-inferiority, they will be 
assessed hierarchically with a two-sided significance level of α = 0.05 at each step, 
ensuring Type I error control via closed testing: 
• Intubation time: if H₀ is rejected, then → 
• POGO: if H₀ is rejected, then → 
• Operator satisfaction. 
 
If at any level H₀ cannot be rejected, the sequence stops and subsequent endpoints 
will not be analyzed confirmatorily. 
Given the anticipated low incidence of adverse events, safety endpoints will be 
considered hypothesis-generating only and will not be subject to confirmatory testing. 
All other secondary endpoints will be classified as exploratory: only effect estimates 
will be reported, without p-values or confidence intervals, with no multiplicity 
adjustment and no confirmatory interpretation. Consequently, no inferential 
conclusions will be drawn from them. 
 
iii. Secondary endpoints 
Outcome 
Statistic 
Hypothesis 
Measure 
Objective 
Overall 
success 
proportion 
Proportion of 
success up to 3 
attempts 
𝐻𝑜: 𝜋𝐿−𝜋𝐶
≤−0.05 
𝐻𝑎: 𝜋𝐿−𝜋𝐶
> −0.05 
Difference in 
proportions, RR, 
NNT (two-sided 
95% CI) 
Exploratory 
POGO 
Mean 
Percentage of 
Glottic Opening 
𝐻𝑜: 𝜇𝐿= 𝜇𝐶 
𝐻𝑎:  𝜇𝐿≠ 𝜇𝐶 
Difference in 
means (95% CI) 
Confirmatory 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
40 
 
Fremantle 
score 
Proportion in 
each ordinal 
category of the 
Fremantle score 
𝐻𝑜: 𝜋𝐿𝐹
=  𝜋𝐶𝐹;  𝐻𝑜: 𝜋𝐿𝑃
=  𝜋𝐶𝑃;  𝐻𝑜: 𝜋𝐿𝑁
=  𝜋𝐶𝑁;  𝐻𝑜: 𝜋𝐿1
=  𝜋𝐶2;  𝐻𝑜: 𝜋𝐿3
=  𝜋𝐶3. 𝐻𝑜: 𝜋𝐿𝐹
=  𝜋𝐶𝐹  
𝐻𝑎: 𝐴𝑙 𝑚𝑒𝑛𝑜𝑠 𝑢𝑛𝑎 
𝜋 𝑒𝑠 ≠0 
Absolute and 
relative 
frequencies of 
proportions 
(95% CI) 
Exploratory 
Intubation time 
Mean in 
seconds 
𝐻𝑜: 𝜇𝐿= 𝜇𝐶 
𝐻𝑎:  𝜇𝐿≠ 𝜇𝐶 
Mean by group 
(SD), difference 
in means (95% 
CI) 
Confirmatory 
Operator 
satisfaction 
Average scores 
per item on the 
Likert scale (1 to 
5) 
𝐻𝑜: 𝜇𝐿= 𝜇𝐶 
𝐻𝑎:  𝜇𝐿≠ 𝜇𝐶 
Mean score by 
group, 
difference in 
means (95% CI) 
Confirmatory 
SAGAT 
Proportion of 
overall loss of 
situational 
awareness 
𝐻𝑜: 𝜋𝐿= 𝜋𝐶 
𝐻𝑎:  𝜋𝐿≠ 𝜋𝐶 
Proportion of 
participants with 
loss of 
situational 
awareness by 
group, 
difference in 
proportions 
(95%) 
Exploratory 
Multinomial 
logistic 
regression for 
SAGAT failure 
and assigned 
group 
Ho: No 
interaction exists 
between 
assigned group 
and SAGAT 
responses 
Ha: Interaction 
exists 
OR of belonging 
to each SAGAT 
response 
category by 
assigned group, 
95% CI 
Adverse 
events (harms) 
Proportion of 
adverse events 
𝐻𝑜: 𝜋𝐿= 𝜋𝐶 
𝐻𝑎:  𝜋𝐿≠ 𝜋𝐶 
RR, RAR, NND, 
difference in 
proportions 
(95% CI) 
Hypothesis-
generating 
Table 6. Statistical analysis plan for secondary outcomes 
 
b. Definition of who will be included in the analysis 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
41 
 
The primary endpoint will be adjudicated under a per-protocol (PP) analysis, defined 
as all randomized participants who: (i) met all eligibility criteria; (ii) received the 
assigned device on the first attempt; (iii) had no prespecified major deviations as listed 
below; and (iv) have a valid measurement of the primary endpoint within the defined 
window. 
Major deviations (trigger PP exclusion): (a) device change before outcome 
measurement; (b) non-permitted third-party intervention; (c) violation of eligibility 
criteria post-randomization; (d) use of co-interventions that impact the outcome; (e) 
absence of primary outcome measurement; (f) crossovers due to execution error; (g) 
exceeding the predefined maximum number of attempts.  
Non-inferiority rule: Non-inferiority will be declared under the per-protocol analysis. 
 
High adherence is anticipated; nevertheless, it could be compromised by major 
deviations such as crossover. To strengthen inference, a sensitivity per-protocol 
analysis will be performed using stabilized inverse probability weighting (IPW) among 
adherent participants (𝐴= 1) within the PP-eligible cohort. Stabilized weights will be 
applied as: 
𝒘𝒊=
𝑷𝒓(𝑨= 𝟏|𝑮𝒊)
𝑷(𝑨= 𝟏)| 𝑮𝒊, 𝑿𝒊), 
 
Where 𝑮 is the assigned group and 𝑿 are baseline pre-procedure covariates related 
to both adherence and the outcome based on clinical relevance and prior literature: 
Mallampati (49), intubator experience (21,69), body mass index (70), thyromental and 
sternomental distances, thyromental height, limited cervical motion (71), ASA 
classification, and other predictors of difficult airway. 
The denominator 𝑷(𝑨= 𝟏)| 𝑮𝒊, 𝑿𝒊) will be modeled with multivariable logistic 
regression: 
𝑙𝑜𝑔𝑖𝑡{𝑃𝑟(𝐴= 1|𝐺, 𝑋)} = 𝑎0 + 𝑎𝑔𝐺+ 𝑎𝑋𝑋, ) 
and the numerator 𝑷𝒓(𝑨= 𝟏|𝑮𝒊) will be the observed proportion of adherent 
participants within each arm. 
Covariate balance after weighting will be evaluated using standardized mean 
differences (SMD), targeting 𝑺𝑴𝑫< 𝟎. 𝟏𝟎 for all covariates. 
The weighted proportions of first-attempt intubation success will be: 
𝑃𝒂
̂ = ∑𝑮𝒊=𝒂,𝑨𝒊=𝟏𝒘𝒊𝒀𝒊
𝒊:
)
∑𝑮𝒊=𝒂,𝑨𝒊=𝟏𝒘𝒊
𝒊:
 
 
And the difference in proportions will be ∆̂= 𝑃̂1 −  𝑃̂0 Confidence intervals will be 
obtained by bootstrap. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
42 
 
Complementarily, an intention-to-treat (ITT) analysis will be conducted, including all 
randomized patients and analyzing them in their originally assigned group, regardless 
of the device ultimately used or any protocol deviations. 
 
c. Handling of missing data 
The expected loss of data is low due to the intraoperative nature of outcome 
assessment; however, two types of missing data are anticipated in this trial: (1) 
missing data for the primary outcome (first-attempt intubation success), mainly related 
to participants who do not complete the assigned procedure (switch of assigned 
device or no intubation), and (2) missing data for secondary outcomes (POGO, 
Fremantle, intubation time, operator satisfaction), which may be due to errors in video 
recording 
or 
loss 
to 
follow-up 
when 
extubation 
is 
postponed. 
To prevent data loss, data will be collected continuously and systematically, using the 
REDCap system to ensure record quality and security. 
For the primary outcome, a per-protocol analysis will be performed; that is, participants 
who are intubated with a device different from the one assigned or who withdraw from 
the trial before the intervention will be excluded from the main analysis so that the 
analysis reflects each device’s performance. 
Given that missing data in secondary outcomes (POGO, Fremantle, etc.) may be 
related to observed variables (device, operator experience), they will be assumed 
MAR (Missing At Random) and handled via multiple imputation (MICE) in R 
statistical software (v4.4.3, R Core Team 2025). 
Variables included in the imputation procedure will be age, sex, device, intubation 
success, intubation time, operator satisfaction, SAGAT, and adverse events. 
Continuous variables that do not meet normality assumptions will be transformed, and 
categorical variables will be treated as factors. 
Multiple imputation will be performed separately for each treatment group, generating 
20 imputed datasets, and results will be combined using Rubin’s Rules. Sensitivity 
analyses will include: (1) complete-case analysis, (2) MAR analysis with imputation, 
and (3) MNAR analysis, assuming that missingness represents negative outcomes. 
 
d. Additional analysis methods   
The performance of the Laringocel and C-MAC D-Blade videolaryngoscopes will be 
evaluated in two prespecified subgroups, following ICEMAN recommendations (72).  
The subgroup analysis will be applied only to the primary outcome (first-attempt 
intubation success), and effect-modifying interaction will be sought. 
A multivariable logistic regression model will be used that includes: 
 
- 
Device (Laringocel or C-MAC D-Blade) 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
43 
 
- 
Subgroup variable (type of muscle relaxant or obesity) 
- 
Interaction term between the device and the subgroup variable 
 
The measure of association will be the odds ratio with its 95% confidence interval (95% 
CI), as well as the absolute success proportion (with 95% CI) for each device within 
each subgroup. 
An interaction will be considered clinically relevant if it is consistent with the a priori 
hypothesis and the p-value of the interaction term is < 0.05.  
This trial is designed to detect an overall difference in the primary outcome between 
videolaryngoscopes. By nature, subgroup analyses are underpowered to detect 
anything but large interaction effects. While we recognize the increased risk of Type I 
error with multiple comparisons, we will not apply a formal multiplicity adjustment, given 
the exploratory nature of these analyses. This limitation will be explicitly addressed in 
the interpretation of results. 
 
The following subgroup analyses are planned:  
(1) Obesity: The performance of the devices will be compared in obese patients (BMI ≥ 
30 kg/m²) and non-obese patients (BMI < 30 kg/m (73).  
Increased tissue mass in the airways and altered anatomy may hinder laryngoscopy. 
Our hypothesis is that videolaryngoscopes may show differential efficacy in obese 
patients compared with non-obese patients. The difference in the success proportion 
between videolaryngoscopes is expected to be more pronounced in obese patients. 
We recognize that the BMI cutoff of 30 kg/m² for obesity is arbitrary. We will perform 
a sensitivity analysis using BMI as a continuous variable to assess the robustness of 
the findings related to obesity. 
 
(2) Type of muscle relaxant: Device performance will be evaluated according to the 
type of muscle relaxant used: depolarizing (succinylcholine) and non-depolarizing 
(rocuronium, vecuronium, cisatracurium). This subgroup analysis is based on 
pharmacological differences among muscle relaxants and their influence on 
intubation conditions (74,75). 
Succinylcholine is expected to provide faster and more complete neuromuscular 
relaxation compared with non-depolarizing agents. Our hypothesis is that 
videolaryngoscope performance may differ when non-depolarizing drugs are used, 
potentially due to variations in the speed and quality of airway exposure. Rocuronium 
is expected to have better results than cisatracurium and vecuronium.  
a. Rocuronium: Rapid onset, intermediate duration. 
b. Vecuronium: Slower onset, intermediate duration. 
c. Cisatracurium: Slow onset, intermediate duration, elimination independent of 
renal/hepatic function. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
44 
 
d. Succinylcholine: Ultra-rapid onset, ultra-short duration. 
 
VIII. Methods: Monitoring 
28. Data Monitoring Committee 
a. Data monitoring 
Due to the nature of this trial —a single, short-duration procedure performed by 
specialists in Anesthesiology as part of routine practice and usual care, which does 
not involve prolonged treatment administration or long-term follow-up— the 
establishment of a Data Monitoring Committee is not considered necessary.  
 
b. Interim analysis 
No interim analyses or interim assessments are planned for this clinical trial. This 
decision is based on the relatively rapid recruitment and the collection of immediate 
intraoperative outcomes.  
 
29. Trial Monitoring  
Because this study is short in duration, with a single intervention and immediate 
outcome collection, independent external audits are not contemplated. Nevertheless, 
internal quality control mechanisms will be implemented, led by the research team, to 
verify protocol compliance. These actions will include: 
• Cross-review every 15 days of the data collection forms. 
• Random verification of records through review of the recorded intubation 
videos. 
All study information will be stored in a database with restricted access control and 
will be available for evaluation by the institutional ethics committee if required. 
Given that there is no external sponsor or institutional/commercial funding, oversight 
and compliance functions will be carried out exclusively by the research team, 
following Good Clinical Practice principles and local ethical guidelines. 
 
 
IX. Ethics 
30. Ethics Committee Approval 
This clinical trial will be conducted in accordance with the principles of the Belmont  
Report—respect for persons, beneficence, and justice (76), the Declaration of Helsinki 
(77) and the 2016 CIOMS Guidelines (78). It will also adhere to harmonized Good 
Clinical Practice ICH E6(R3). In the Colombian context, current regulations will be 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
45 
 
followed, in particular Resolution 8430 of 1993 of the Ministry of Health and the 
personal data protection regime (Law 1581 of 2012 and Decree 1377 of 2013) (79,80).  
The study design and conduct will be evaluated against the seven ethical requirements 
proposed by Emanuel et al.—social value, scientific validity, fair subject selection, 
favorable risk–benefit ratio, independent review, informed consent, and respect for 
participants — (81). 
The protocol will be reviewed and approved by the Research Ethics Committee of 
Hospital Alma Máter de Antioquia, within the framework of the master’s thesis of the 
Master’s Program in Clinical Epidemiology at the University of Antioquia.  
In accordance with the Belmont principles, respect for persons and autonomy will be 
ensured through free and informed consent that is clear and understandable, explaining 
the research nature of the project, voluntary participation, random assignment of the 
device, and the patient’s right to withdraw at any time without affecting their usual medical 
care.  
In terms of benefits for participants, videolaryngoscopes will be used in both arms. The 
anesthesiology literature recognizes them as a first-line strategy for orotracheal 
intubation, being associated with higher first-attempt success rates and a lower probability 
of failed intubation compared with direct laryngoscopy, which would be a device likely 
chosen in the absence of the trial. Videolaryngoscopes are routine practice, have INVIMA 
registration, and do not entail procedures beyond what the patient would receive as part 
of standard care. Additionally, patients will be closely followed by the research team from 
their initial assessment through the post-extubation evaluation, which will allow timely 
detection of difficult airway and oral cavity injuries. If any of the above are detected, timely 
referral to the appropriate services will be ensured. 
With respect to the technological niche in Medellín and Colombia, the trial will generate 
local comparative clinical evidence on the performance of a videolaryngoscope 
developed and assembled in the country. This information will be valuable for acquisition 
decision-making, for the formulation of institutional policies, and for recommendations in 
clinical practice guidelines. Likewise, access to new technologies may extend to the 
training of medical students, general practitioners, and residents in anesthesiology, critical 
care, and emergency medicine. Regarding scientific output, the study contemplates 
public data registration, publication of a scientific article, and the availability of an 
anonymized dataset for secondary research, subject to ethics approval and data use 
agreements.  
The principle of nonmaleficence is preserved because, in the event of failure of the 
assigned device or if the anesthesiologist considers that patient safety could be 
compromised, the protocol allows an immediate switch to an alternative intubation 
strategy without the need to withdraw the participant. Standardized monitoring of adverse 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
46 
 
events is also maintained during the intraoperative period and in the immediate 
postoperative period. Standardized adverse event surveillance will be implemented 
(mandatory capnography and clinical evaluation after extubation), always ensuring 
patient safety. 
The study contributes to the principle of justice because it seeks to answer a research 
question that may have a direct impact on populations with limited resources by 
evaluating a domestically produced device (Laringocel) that is potentially more accessible 
and economical compared with higher-cost international alternatives. Additionally, 
Colombian clinical practice guidelines recommend the use of this device and 
acknowledge its economic limitations. 
Risk classification and risk/benefit analysis 
With regard to risk classification, in accordance with Resolution 8430 of 1993, this trial is 
considered to involve greater-than-minimal risk, given that an intervention is performed 
on patients. However, participation in the study does not expose patients to risks beyond 
those inherent to orotracheal intubation—a procedure that is part of standard clinical 
practice in anesthesia. The potential risks related to videolaryngoscopy have been 
identified and limited. 
Risks of the intubation procedure (common to both arms): Transient hypoxemia, 
esophageal intubation, transient pharyngolaryngeal symptoms such as sore throat, 
hoarseness, or cough, and dental trauma. All of these events are described as infrequent 
(see section on expected adverse events), self-limited in most cases, and manageable 
by the clinical team (10,44,50). Low and comparable frequencies between arms are 
expected, as both are hyperangulated videolaryngoscopes operated by trained clinicians. 
No serious adverse events or significant harm attributable to the intervention are 
anticipated. 
The potential benefits (common to both arms) outweigh these risks, as participants 
will have access to first-line airway devices, with a higher probability of first-attempt 
success, a lower proportion of esophageal intubation, and reductions in failed intubation 
and postoperative pharyngolaryngeal symptoms compared with direct laryngoscopy. In 
addition, there is the indirect benefit of close monitoring by the research team, systematic 
verification of placement (continuous capnography), active AE recording, and timely 
management; and at the societal level, the trial will generate local evidence on the 
effectiveness and safety of a device developed in Colombia, potentially more accessible 
to the health system, with an impact on equity and availability.  
Risk control: 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
47 
 
Risk 
Source 
Expected 
probability 
Mitigations 
Residual risk 
Transient hypoxemia 
Intubation time, 
desaturation 
Low 
Preoxygenation, limit of 
three attempts, 
capnography, rescue 
plan 
Low 
Esophageal intubation 
Trajectory error 
Low 
Glottic visualization, 
stylet, mandatory ETCO₂ 
Very low 
Oropharyngeal/dental 
trauma 
Levering, contact with 
teeth/tissues 
Very low 
VL technique without 
levering, anesthesiologist 
with CUSUM 
Very low 
Device failure 
Optics/condensation 
Very low 
Pre-procedure functional 
check, backup device 
Very low 
 
The assessment of this information and its therapeutic impact will be at the sole discretion 
of the treating clinical team. In line with the bioethical principles established in the 
Declaration of Helsinki, the research team reaffirms its commitment to seeking the 
greatest possible benefit for patients. Any information generated during the procedure 
that has immediate clinical relevance will be communicated in real time to the care team, 
without waiting for the final analysis of the study. The interpretation and potential 
therapeutic implementation of such information will be the exclusive responsibility of the 
treating clinical team. 
Regarding participant selection, the inclusion and exclusion criteria do not entail targeted 
selection of vulnerable populations. The intubation procedure under evaluation 
constitutes a routine component of anesthetic management, performed by trained 
professionals under controlled conditions. Individuals such as general physicians, 
residents, and medical students are excluded as intervention administrators. Participation 
in the study does not modify the usual course of care nor alter the clinical indications for 
orotracheal intubation. 
The research group undertakes to adhere strictly to a rigorous methodological design, 
ensuring the quality of the data collected and of the inferences derived from them. 
Likewise, the protocol will remain under the continuous oversight and scrutiny of the 
technical and ethics committees for research. We consider the participation of external 
evaluators indispensable, as from an independent perspective they can identify 
opportunities for improvement and ensure that the principles guiding this study are upheld 
throughout its execution. 
Transparent dissemination of the results and their public registration on ClinicalTrials.gov 
are anticipated once the corresponding approvals are obtained. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
48 
 
In summary, the risk–benefit balance is favorable: foreseeable risks are infrequent and 
mitigable, while the potential benefits—both for participants and for the medical 
community and the health system—are pertinent and socially valuable. 
31. Protocol Amendments  
Any modification to the protocol that could impact study conduct, participant safety, 
potential benefit, or ethical integrity (including changes to objectives, eligibility criteria, 
sample size, procedures, outcomes, or statistical analyses) will be considered a protocol 
amendment. 
These modifications will require review and approval by the Research Ethics Committee 
of Hospital Alma Máter de Antioquia. 
Amendments will be communicated to all stakeholders prior to implementation, including 
the research team, ethics committees, and public registries on ClinicalTrials.gov. 
All protocol versions will be uniquely identified by a version number and update date. 
 
32. Informed Consent  
a. Who will obtain informed consent and how 
The investigator responsible for recruitment will disclose and obtain informed consent. 
Prior to enrollment in the trial, all candidates will receive a clear and comprehensive 
explanation of the research nature, detailing the study objectives, expected social and 
participant benefits, procedures, possible risks (mucosal injury, dental loss, or pharyngeal 
pain), and the possibility of withdrawing at any time without repercussions on their medical 
care. 
The process will be complemented by provision of a written informed consent document, 
which will be read together with the participant. Consent will be signed by the participant 
before any study-related procedure and will be filed in the trial documentation. 
 
b. Biological samples  
No biological samples will be collected from participants. However, data gathered during 
the study—including clinical, video, and outcome information—may be used in future 
research that meets ethical requirements. 
Participants will be informed that their data may be used for additional research 
purposes. The consent form will include a specific option for participants to grant or 
decline consent for future use of their data. Those who grant consent may withdraw it at 
any time by contacting the principal investigator directly. 
Data will be anonymized and stored on the REDCap platform. These data will be 
retained for a minimum of five years after study completion, ensuring their integrity and 
availability for future research. 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
49 
 
Only the principal investigator (GRM) and authorized personnel will have access to 
identifiable data, whereas investigators participating in future studies will only be able to 
access anonymized data. 
Access to data for future research will be subject to approval by the Research Ethics 
Committee. Investigators wishing to use these data must submit a formal request 
describing the study objective and ensuring compliance with ethical requirements. 
33. Confidentiality 
Access to data will require a personal, non-transferable password granted following 
approval by the ethics and technical committees of Hospital Alma Máter de Antioquia for 
the REDCap database. 
Electronic data will be managed through the institutional REDCap platform, which has 
encryption systems and password-controlled access. 
Only the authorized research team will have access to the information, which will be 
handled confidentially. 
Study results will be reported without including information that would allow participant 
identification 
 
34. Ancillary and Post-Trial Care  
This trial evaluates videolaryngoscopy devices that are part of the usual armamentarium 
available to anesthesiologists, without introducing experimental interventions beyond 
standard clinical practice. Therefore, no additional ancillary care needs are anticipated 
as a result of participation in the trial. 
If any adverse event occurs during the procedure, it will be managed by the responsible 
medical team as part of standard care. 
 
X. Appendices 
 
35.  Appendix B. PRECIS  
 
a. Step 1: What design approach are you adopting? 
The stance regarding the trial focuses on answering whether the Laringocel 
videolaryngoscope is non-inferior under usual clinical practice conditions, 
compared with C-MAC® D-BLADE. The design aims for a pragmatic 
approach. 
b. Step 2: Consider your trial design options for each PRECIS-2 domain 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
50 
 
c. Step 3: Score the options chosen in Step 2 from 1 to 5 and plot on the PRECIS-
2 wheel 
a. 1. Very explanatory 
b. 2. Rather explanatory 
c. 3. Equally pragmatic and explanatory 
d. 4. Rather pragmatic 
e. 5. Very pragmatic 
Item 
Rating 
Justification 
Eligibility 
4 
The trial will include patients who reflect usual care conditions in the 
context of orotracheal intubation, specifically those scheduled for elective 
surgery under general anesthesia. However, patients with an anticipated 
difficult airway will be excluded, since this scenario shifts the context from 
intubation under general anesthesia to awake intubation. Although these 
patients could potentially benefit from the intervention, they will not be 
considered in this trial due to differences in the clinical conditions and 
technical requirements. 
Recruitment 
5 
Patients will be selected directly from the usual surgical scheduling flow 
at Hospital Alma Máter, either on the same day their elective surgeries are 
scheduled or at the pre-anesthesia consultation. No campaigns or 
additional efforts will be undertaken to recruit participants outside this 
context. 
Setting 
5 
Hospital Alma Máter de Antioquia, a tertiary-level center serving urban 
and rural populations primarily from the department of Antioquia, 
Colombia, caring for individuals covered by both contributory and 
subsidized health schemes. 
Organization 
4 
The organization of the trial largely coincides with usual practice, since 
the personnel involved are anesthesiologists with standard specialized 
training in airway management and videolaryngoscopy. However, 
videolaryngoscopy is not a routine component of all operating rooms in 
Colombia; therefore, in centers that do not have the device, acquisition or 
arrangement of this additional resource will be required. 
Flexibility in 
delivery of the 
intervention 
4 
Administration of the intervention will allow standard patient care with 
respect 
to 
anesthetic 
induction. 
Clinical 
judgment 
will 
guide 
neuromuscular relaxation (drug and dose). The time to initiate intubation 
is specified according to the drug chosen; this does not depart from what 
a trained anesthesiologist normally does. 
Up to three attempts with the same technique are allowed, and switching 
devices or performing additional maneuvers is permitted at the 
anesthesiologist’s discretion, reflecting the flexibility of routine care. 
There are no restrictions on co-interventions, allowing the professional to 
apply any complementary measures deemed appropriate. 
 
For monitoring, a basic record of the procedure will be kept (number of 
attempts, assigned technique, intubation time, procedure video, and any 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
51 
 
device change or maneuver) and drug administration. 
Flexibility in 
adherence 
3 
The trial mandates use of the assigned device on the first attempt and 
classifies as major deviations any device change, third-party intervention, 
or non-permitted co-interventions, which leads to exclusion from the per-
protocol analysis. In addition, we standardized the procedure and 
required training with competency verification (CUSUM), measures that 
enhance adherence beyond routine practice. However, protocol 
deviations at the anesthesiologist’s discretion are permitted. 
Follow-up 
4 
For the primary outcome, no follow-up will be conducted after delivery of 
the intervention; however, the adverse event (safety) outcome entails 
follow-up 1 hour after extubation, which often is not part of usual care and 
represents additional personnel. No additional follow-up is planned for the 
other outcomes. 
Primary outcome 
4 
The primary outcome will be first-attempt intubation success. Its 
importance lies in avoiding multiple intubation attempts and potential 
associated complications, which directly impacts patient safety (7,12). In 
addition, it is a commonly used indicator as a quality metric in both clinical 
practice and research (82). However, although it is highly relevant to 
anesthetic practice, it is not as directly patient-centered as outcomes tied 
to the patient’s experience or postoperative recovery. 
Primary analysis 
4 
Primary outcome analysis will be per protocol because this is a non-
inferiority trial; however, intention-to-treat sensitivity analyses will be 
performed. 
Table 7. PRECIS-2 ratings 
 
d. Step 4: Review the PRECIS-2 wheel 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
52 
 
 
Figure 2. PRECIS-2 graphical tool. Taken and adapted from: Loudon K, et al. The PRECIS-
2 tool designing trials that are fit for purpose. BMJ;350:h2147 
 
36. Appendix C. List of operational sites. 
Site name 
Address 
Site type 
Number of operating 
rooms 
Services included in the 
trial 
Assigned investigators 
Hospital Alma Máter – 
Hospital-based 
Calle 
69 
#51C–24, 
Medellín, 
Sevilla 
neighborhood 
High-complexity 
hospital 
14 operating rooms 
Main recruitment center 
 
Hospital Alma Máter – 
Ambulatory site 
Carrera 
51A 
#62–42, 
Medellín, 
Prado 
neighborhood 
Ambulatory 
surgical 
center 
4 operating rooms 
 
 
 
37. Appendix D. Operational table of variables 
Variable 
Operational definition 
Nature 
Scale 
Unit or code 
eda 
Age 
Quantitative 
continuous 
Ratio 
Years 
gen 
Gender 
Qualitative 
Nominal 
0. Female; 1. Male 
pes 
Weight 
Quantitative 
continuous 
Ratio 
Kilograms (kg) 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
53 
 
tal 
Height 
Quantitative 
continuous 
Ratio 
Centimeters (cm) 
imc 
Body mass index (BMI) 
Quantitative 
continuous 
Ratio 
Kilograms per 
square meter 
(kg/m²) 
pro 
Place of residence 
Qualitative 
Nominal 
0. Rural; 1. Urban 
mal 
Mallampati 
Qualitative 
Ordinal 
1. I; 2. II; 3. III; 4. IV 
pre 
Number of previous surgeries 
Quantitative 
discrete 
Ratio 
Integer 
den 
Dentition status 
Qualitative 
Ordinal 
0. Good; 1. Poor; 2. 
Edentulous 
asa 
ASA classification 
Qualitative 
Ordinal 
1. I; 2. II; 3. III; 4. IV; 
5. V; 6. VI 
sta 
Patient status 
Qualitative 
Nominal 
0. Outpatient; 1. 
Inpatient 
rie 
Surgical risk 
Qualitative 
Ordinal 
0. Low risk; 1. 
Moderate risk; 2. 
High risk 
mod 
Surgical specialty/model 
Qualitative 
Nominal 
0. General surgery; 
1. Orthopedic; 2. 
Urologic; 3. 
Gynecologic; 4. 
Neurosurgical; 5. 
Plastic surgery; 6. 
Otorhinolaryngolog
y; 7. 
Ophthalmology; 8. 
Vascular; 9. Other 
tec 
General anesthesia technique 
Qualitative 
Nominal 
1. Balanced — 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
54 
 
halogenated 
agents; 2. Total 
intravenous 
tq 
Surgery time 
Quantitative 
continuous 
Ratio 
Minutes (min) 
ta 
Anesthesia time 
Quantitative 
continuous 
Ratio 
Minutes (min) 
ti 
Intubation time 
Quantitative 
continuous 
Ratio 
Seconds (s) 
lar 
Type of laryngoscope used 
Qualitative 
Nominal 
0. C-MAC; 1. 
Laringocel; 2. 
Direct 
laryngoscope 
pog 
Percentage of Glottic Opening 
(POGO) 
Quantitative 
continuous 
Ratio 
0 to 100% 
nii 
Number of intubation 
attempts 
Quantitative 
discrete 
Ratio 
Integer 
Frv 
Best laryngeal view 
(Fremantle) 
Qualitative 
Ordinal 
F = Full; P = Partial; 
N = Not visible 
frf 
Ease of intubation (Fremantle) 
Qualitative 
Ordinal 
1. Easy; 2. 
Modified; 3. 
Unattainable 
sat 
Operator satisfaction 
Qualitative 
Ordinal 
1–5 
sgp 
Perception (SAGAT) 
Qualitative 
Dichotomous 
1. Yes; 2. No 
sgc 
Comprehension (SAGAT) 
Qualitative 
Dichotomous 
1. Yes; 2. No 
sgy 
Projection (SAGAT) 
Qualitative 
Dichotomous 
(with open-
1. Yes; 2. No 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
55 
 
ended 
description if 
applicable) 
ext 
Place of extubation 
Qualitative 
Nominal 
1. Operating room; 
2. ICU; 3. Recovery 
room; 4. Inpatient 
ward; 5. Other 
adv 
Dental loss (Adverse event) 
Qualitative 
Dichotomous 
1. Yes; 2. No 
adl 
Mucosal injury (Adverse event) Qualitative 
Dichotomous 
1. Yes; 2. No 
add 
Postoperative sore throat 
(Adverse event) 
Qualitative 
Dichotomous 
1. Yes; 2. No 
tmd 
Thyromental distance 
Quantitative 
continuous 
Ratio 
Centimeters (cm) 
srd 
Sternomental distance 
Quantitative 
continuous 
Ratio 
Centimeters (cm) 
tmh 
Thyromental height 
Quantitative 
continuous 
Ratio 
Millimeters (mm) 
nc 
Neck circumference 
Quantitative 
continuous 
Ratio 
Centimeters (cm) 
iid  
Inter-incisor distance 
Quantitative 
continuous 
Ratio 
Centimeters (cm) 
csm 
Cervical spine mobility n 
Qualitative 
Ordinal 
1. Normal; 2. 
Reduced; 3. Fixed 
upt 
Upper-lip bite test 
Qualitative 
nominal 
I-III 
 
 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
56 
 
XI. References  
1. SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials | 
The BMJ [Internet]. [cited 2025 May 11]. Available from: 
https://www.bmj.com/content/389/bmj-2024-081660.full 
2. Piaggio G, Elbourne DR, Pocock SJ, Evans SJW, Altman DG, CONSORT Group  for the. Reporting 
of Noninferiority and Equivalence Randomized Trials: Extension of the CONSORT 2010 
Statement. JAMA. 2012 Dec 26;308(24):2594–604.  
3. Cook TM, Woodall N, Frerk C. Major complications of airway management in the UK: results of 
the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway 
Society. Part 1: Anaesthesia†. Br J Anaesth. 2011 May 1;106(5):617–31.  
4. Cook TM, Oglesby F, Kane AD, Armstrong RA, Kursumovic E, Soar J. Airway and respiratory 
complications during anaesthesia and associated with peri-operative cardiac arrest as 
reported to the 7th National Audit Project of the Royal College of Anaesthetists. Anaesthesia. 
2024;79(4):368–79.  
5. Peterson GN, Domino KB, Caplan RA, Posner KL, Lee LA, Cheney FW. Management of the 
Difficult Airway: A Closed Claims Analysis. Anesthesiology. 2005 July 1;103(1):33–9.  
6. Apfelbaum JL, Hagberg CA, Connis RT, Abdelmalak BB, Agarkar M, Dutton RP, et al. 2022 
American Society of Anesthesiologists Practice Guidelines for Management of the Difficult 
Airway*. Anesthesiology. 2022 Jan 1;136(1):31–81.  
7. Law JA, Duggan LV, Asselin M, Baker P, Crosby E, Downey A, et al. Canadian Airway Focus 
Group updated consensus-based recommendations for management of the difficult airway: 
part 1. Difficult airway management encountered in an unconscious patient. Can J Anesth Can 
Anesth. 2021 Sept 1;68(9):1373–404.  
8. Rose DK, Cohen MM. The airway: problems and predictions in 18,500 patients. Can J Anaesth. 
1994 May 1;41(5):372–83.  
9. Crosby ET, Cooper RM, Douglas MJ, Doyle DJ, Hung OR, Labrecque P, et al. The unanticipated 
difficult airway with recommendations for management. Can J Anaesth. 1998 Aug 1;45(8):757–
76.  
10. Hansel J, Rogers AM, Lewis SR, Cook TM, Smith AF. Videolaryngoscopy versus direct 
laryngoscopy for adults undergoing tracheal intubation - Hansel, J - 2022 | Cochrane Library. 
[cited 2024 Oct 24]; Available from: 
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011136.pub3/full 
11. Zhang J, Jiang W, Urdaneta F. Economic analysis of the use of video laryngoscopy versus direct 
laryngoscopy in the surgical setting. J Comp Eff Res. 2021 July;10(10):831–44.  
12. Mort TC. Emergency Tracheal Intubation: Complications Associated with Repeated 
Laryngoscopic Attempts. Anesth Analg. 2004 Aug;99(2):607.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
57 
 
13. Crosby ET, Duggan LV, Finestone PJ, Liu R, Gorter RD, Calder LA. Anesthesiology airway-related 
medicolegal cases from the Canadian Medical Protection Association. Can J Anaesth. 2020 
Nov 16;68(2):183.  
14. Heidegger T. Management of the Difficult Airway. N Engl J Med. 2021 May 12;384(19):1836–47.  
15. Joffe AM, Aziz MF, Posner KL, Duggan LV, Mincer SL, Domino KB. Management of difficult 
tracheal intubation: a closed claims analysis. Anesthesiology. 2019 Oct;131(4):818.  
16. Aziz MF, Brambrink AM, Healy DW, Willett AW, Shanks A, Tremper T, et al. Success of 
Intubation Rescue Techniques after Failed Direct Laryngoscopy in Adults: A Retrospective 
Comparative Analysis from the Multicenter Perioperative Outcomes Group. Anesthesiology. 
2016 Oct;125(4):656–66.  
17. Shiga T, Wajima Z, Inoue T, Sakamoto A. Predicting Difficult Intubation in Apparently Normal 
Patients: A Meta-analysis of Bedside Screening Test Performance. Anesthesiology. 2005 Aug 
1;103(2):429–37.  
18. Xia M, Ma W, Zuo M, Deng X, Xue F, Battaglini D, et al. Expert consensus on difficult airway 
assessment. Hepatobiliary Surg Nutr. 2023 Aug 8;12(4):545.  
19. Nørskov AK, Rosenstock CV, Wetterslev J, Astrup G, Afshari A, Lundstrøm LH. Diagnostic 
accuracy of anaesthesiologists’ prediction of difficult airway management in daily clinical 
practice: a cohort study of 188 064 patients registered in the Danish Anaesthesia Database. 
Anaesthesia. 2015;70(3):272–81.  
20. Piepho T, Kriege M, Byhahn C, Cavus E, Dörges V, Ilper H, et al. German guidelines for airway 
management 2023. Anaesthesiol [Internet]. 2024 May 16 [cited 2024 Sept 30]; Available from: 
https://doi.org/10.1007/s00101-024-01413-5 
21. Pieters BMA, Maas EHA, Knape JTA, van Zundert A a. J. Videolaryngoscopy vs. direct 
laryngoscopy use by experienced anaesthetists in patients with known difficult airways: a 
systematic review and meta-analysis. Anaesthesia. 2017;72(12):1532–41.  
22. Lee J, Cho Y, Kim W, Choi KS, Jang BH, Shin H, et al. Comparisons of Videolaryngoscopes for 
Intubation Undergoing General Anesthesia: Systematic Review and Network Meta-Analysis of 
Randomized Controlled Trials. J Pers Med. 2022 Feb 26;12(3):363.  
23. Saul SA, Ward PA, McNarry AF. Airway Management: The Current Role of Videolaryngoscopy. J 
Pers Med. 2023 Aug 29;13(9):1327.  
24. Levitan RM, Heitz JW, Sweeney M, Cooper RM. The Complexities of Tracheal Intubation With 
Direct Laryngoscopy and Alternative Intubation Devices. Ann Emerg Med. 2011 Mar 
1;57(3):240–7.  
25. Jong AD, Sfara T, Pouzeratte Y, Pensier J, Rolle A, Chanques G, et al. Videolaryngoscopy as a 
first-intention technique for tracheal intubation in unselected surgical patients: a before and 
after observational study. Br J Anaesth. 2022 Oct 1;129(4):624–34.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
58 
 
26. Howard-Quijano KJ, Huang YM, Matevosian R, Kaplan MB, Steadman RH. Video-assisted 
instruction improves the success rate for tracheal intubation by novices. Br J Anaesth. 2008 
Oct 1;101(4):568–72.  
27. Chrimes N, Higgs A, Hagberg CA, Baker PA, Cooper RM, Greif R, et al. Preventing unrecognised 
oesophageal intubation: a consensus guideline from the Project for Universal Management of 
Airways and international airway societies*. Anaesthesia. 2022;77(12):1395–415.  
28. Frerk C, Mitchell VS, McNarry AF, Mendonca C, Bhagrath R, Patel A, et al. Difficult Airway 
Society 2015 guidelines for management of unanticipated difficult intubation in adults. BJA Br J 
Anaesth. 2015 Nov 10;115(6):827.  
29. Marshall SD, Pandit JJ. Radical evolution: the 2015 Difficult Airway Society guidelines for 
managing unanticipated difficult or failed tracheal intubation. Anaesthesia. 2016;71(2):131–7.  
30. Wong DJN, El-Boghdadly K, Owen R, Johnstone C, Neuman MD, Andruszkiewicz P, et al. 
Emergency Airway Management in Patients with COVID-19: A Prospective International 
Multicenter Cohort Study. Anesthesiology. 2021 Apr 13;135(2):292.  
31. Choi GJ. The golden era of videolaryngoscopy: costs we should consider. Korean J Anesthesiol. 
2022 Aug;75(4):293–4.  
32. NICE NI for H and CE. Video laryngoscopes to help intubation in people with difficult airways. 
Medtech Innov Brief [Internet]. 2018 Dec 19. Available from: 
https://www.nice.org.uk/guidance/mib167 
33. Zaouter C, Calderon J, Hemmerling TM. Videolaryngoscopy as a new standard of care. Br J 
Anaesth. 2015 Feb 1;114(2):181–3.  
34. Arteaga IM. Update on difficult airway management with a proposal of a simplified algorithm, 
unified and applied to our daily clinical practice. Colomb J Anesthesiol. 2018 Jan 1;46(1):55–64.  
35. Trivedi JN. An economical model for mastering the art of intubation with different video 
laryngoscopes. Indian J Anaesth. 2014 Aug;58(4):394.  
36. Landing | Laringocel [Internet]. [cited 2024 Oct 25]. Available from: 
https://www.laringocel.com/ 
37. Kleine-Brueggeney M, Greif R, Schoettker P, Savoldelli GL, Nabecker S, Theiler LG. Evaluation 
of six videolaryngoscopes in 720 patients with a simulated difficult airway: a multicentre 
randomized controlled trial. Br J Anaesth. 2016 May 1;116(5):670–9.  
38. Biro P, Schlaepfer M. Tracheal intubation with channeled vs. non-channeled 
videolaryngoscope blades. Romanian J Anaesth Intensive Care. 2018 Oct;25(2):97–101.  
39. Kaplan MB, Ward DS, Berci G. A new video laryngoscope—an aid to intubation and teaching. J 
Clin Anesth. 2002 Dec 1;14(8):620–6.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
59 
 
40. Paolini JB, Donati F, Drolet P. Review article: Video-laryngoscopy: another tool for difficult 
intubation or a new paradigm in airway management? Can J Anesth Can Anesth. 2013 Feb 
1;60(2):184–91.  
41. Lees M, Seal RF, Spady D, Csanyi-Fritz Y, Robinson JL. Randomized trial of success of pediatric 
anesthesiologists learning to use two video laryngoscopes. Pediatr Anesth. 2013;23(5):435–9.  
42. Berkow LC, Morey TE, Urdaneta F. The Technology of Video Laryngoscopy. Anesth Analg. 2018 
May;126(5):1527.  
43. de Carvalho CC, da Silva DM, Lemos VM, dos Santos TGB, Agra IC, Pinto GM, et al. 
Videolaryngoscopy vs. direct Macintosh laryngoscopy in tracheal intubation in adults: a ranking 
systematic review and network meta-analysis. Anaesthesia. 2022;77(3):326–38.  
44. Tosh P, Kadapamannil D, Rajan S, Narayani N, Kumar L. Effect of C-MAC Video Laryngoscope-
aided intubations Using D-Blade on Incidence and Severity of Postoperative Sore Throat. 
Anesth Essays Res. 2018 Mar;12(1):140.  
45. Aziz MF, Abrons RO, Cattano D, Bayman EO, Swanson DE, Hagberg CA, et al. First-Attempt 
Intubation Success of Video Laryngoscopy in Patients with Anticipated Difficult Direct 
Laryngoscopy: A Multicenter Randomized Controlled Trial Comparing the C-MAC D-Blade 
Versus the GlideScope in a Mixed Provider and Diverse Patient Population. Anesth Analg. 2016 
Mar;122(3):740–50.  
46. Kumar KR, Sinha R, Mandal P, Chowdhury AR. C-MAC® D-BLADE for awake oro-tracheal 
intubation with minimal mouth opening – A safe alternative to fibreoptic bronchoscope. Indian 
J Anaesth. 2018 Nov;62(11):916–8.  
47. Health C for D and R. FDA. FDA; 2023 [cited 2024 Dec 5]. Classify Your Medical Device. 
Available from: https://www.fda.gov/medical-devices/overview-device-regulation/classify-
your-medical-device 
48. Premarket Notification 510(k) | FDA [Internet]. [cited 2024 Dec 5]. Available from: 
https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-
correct-submission/premarket-notification-510k 
49. Hypes CD, Stolz U, Sakles JC, Joshi RR, Natt B, Malo J, et al. Video Laryngoscopy Improves 
Odds of First-Attempt Success at Intubation in the Intensive Care Unit. A Propensity-matched 
Analysis. Ann Am Thorac Soc. 2016 Mar;13(3):382–90.  
50. Araújo B, Rivera A, Martins S, Abreu R, Cassa P, Silva M, et al. Video versus direct laryngoscopy 
in critically ill patients: an updated systematic review and meta-analysis of randomized 
controlled trials. Crit Care. 2024 Jan 2;28:1.  
51. Cuzick J, Sasieni P. Interpreting the results of noninferiority trials—a review. Br J Cancer. 2022 
Nov;127(10):1755–9.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
60 
 
52. Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB. Fundamentals of Clinical 
Trials [Internet]. Cham: Springer International Publishing; 2015 [cited 2025 Mar 24]. Available 
from: https://link.springer.com/10.1007/978-3-319-18539-2 
53. Hróbjartsson A, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, et al. SPIRIT 2025 
explanation and elaboration: updated guideline for protocols of randomised trials. 2025 Apr 28 
[cited 2025 May 9]; Available from: https://www.bmj.com/content/389/bmj-2024-081660.full 
54. Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. Better reporting of 
interventions: template for intervention description and replication (TIDieR) checklist and 
guide. 2014 Mar 7 [cited 2025 Mar 26]; Available from: 
https://www.bmj.com/content/348/bmj.g1687.long 
55. C-MAC Video Laryngoscope D-BLADE | KARL STORZ Endoskope | United States [Internet]. 
[cited 2025 Feb 6]. Available from: https://www.karlstorz.com/us/en/product-detail-
page.htm?productID=1000111723&cat=1000071971 
56. Burbano MAZ. AnestesiaR. 2022 [cited 2025 Mar 26]. Habilidades no técnicas en 
Anestesiología: Una revisión narrativa. Available from: 
https://anestesiar.org/2022/habilidades-no-tecnicas-en-anestesiologia-una-revision-
narrativa/ 
57. Mishra A, Catchpole K, Dale T, McCulloch P. The influence of non-technical performance on 
technical outcome in laparoscopic cholecystectomy. Surg Endosc. 2008 Jan;22(1):68–73.  
58. Sobre Sellado | Calculadora de potencia para un ensayo de no inferioridad con resultados 
binarios [Internet]. [cited 2025 Apr 2]. Available from: Sealed Envelope Ltd. 2012. Power 
calculator for binary outcome non-inferiority trial. [Online] Available from: 
https://www.sealedenvelope.com/power/binary-noninferior/ [Accessed Wed Apr 02 2025]. 
59. Sakles JC, Ross C, Kovacs G. Preventing unrecognized esophageal intubation in the emergency 
department. JACEP Open. 2023 June;4(3):e12951.  
60. Levitan RM, Ochroch EA, Rush S, Shofer FS, Hollander JE. Assessment of Airway Visualization: 
Validation of the Percentage of Glottic Opening (POGO) Scale. Acad Emerg Med. 
1998;5(9):919–23.  
61. Ochroch EA, Hollander JE, Kush S, Shofer FS, Levitan RM. Assessment of laryngeal view: 
Percentage of glottic opening scorevs Cormack and Lehane grading. Can J Anaesth. 1999 Oct 
1;46(10):987–90.  
62. O’Loughlin EJ, Swann AD, English JD, Ramadas R. Accuracy, intra- and inter-rater reliability of 
three scoring systems for the glottic view at videolaryngoscopy. Anaesthesia. 2017;72(7):835–
9.  
63. The Development and Preliminary Evaluation of a Proposed New Scoring System for 
Videolaryngoscopy [Internet]. [cited 2025 Feb 25]. Available from: 
https://journals.sagepub.com/doi/epdf/10.1177/0310057X1204000417 

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
61 
 
64. Rendeki S, Keresztes D, Woth G, Mérei Á, Rozanovic M, Rendeki M, et al. Comparison of 
VividTrac®, Airtraq®, King Vision®, Macintosh Laryngoscope and a Custom-Made 
Videolaryngoscope for difficult and normal airways in mannequins by novices. BMC 
Anesthesiol. 2017 May 26;17:68.  
65. Endsley MR. A Systematic Review and Meta-Analysis of Direct Objective Measures of Situation 
Awareness: A Comparison of SAGAT and SPAM. Hum Factors J Hum Factors Ergon Soc. 2021 
Feb;63(1):124–50.  
66. Non-Inferiority Tests for the Difference Between Two Proportions.  
67. Rothmann MD, Wiens BL, Chan ISF. Design and Analysis of Non-Inferiority Trials [Internet]. 0 
ed. Chapman and Hall/CRC; 2016 [cited 2025 Mar 24]. Available from: 
https://www.taylorfrancis.com/books/9781584888055 
68. Sotres-Ramos D, Almendra-Arao F, Ramírez-Figueroa C. Exact Critical Values for Farrington-
Manning Noninferiority Exact Test. Drug Inf J. 2010 Mar;44(2):159–64.  
69. Hansel J, Rogers AM, Lewis SR, Cook TM, Smith AF. Videolaryngoscopy versus direct 
laryngoscopy for adults undergoing tracheal intubation - Hansel, J - 2022 | Cochrane Library. 
[cited 2024 Sept 26]; Available from: 
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011136.pub3/full 
70. Gil-Bazán SD, Vásquez-Tirado GA, Chávez-Cruzado E, Meregildo-Rodríguez ED, Quispe-
Castañeda CV, Guzmán-Aguilar WM, et al. Videolaryngoscopy vs. direct laryngoscopy in 
orotracheal intubation in obese critical patients: Systematic review and meta-analysis. Med 
Intensiva Engl Ed [Internet]. Available from: https://www.medintensiva.org/en-
videolaryngoscopy-vs-direct-laryngoscopy-in-avance-S2173572725000438 
71. Song SE, Jung JY, Jung CW, Park JY, Kim WH, Yoon HK. First-pass success rate and predictive 
factors for stylet use in videolaryngoscopic intubations with a Macintosh blade: a prospective 
observational study. Can J Anesth Can Anesth. 2025 May 1;72(5):758–67.  
72. Schandelmaier S, Briel M, Varadhan R, Schmid CH, Devasenapathy N, Hayward RA, et al. 
Development of the Instrument to assess the Credibility of Effect Modification Analyses 
(ICEMAN) in randomized controlled trials and meta-analyses. CMAJ Can Med Assoc J. 2020 Aug 
10;192(32):E901–6.  
73. Yakushiji H, Goto T, Shirasaka W, Hagiwara Y, Watase H, Okamoto H, et al. Associations of 
obesity with tracheal intubation success on first attempt and adverse events in the emergency 
department: An analysis of the multicenter prospective observational study in Japan. PLoS 
ONE. 2018 Apr 19;13(4):e0195938.  
74. Plaud B, Baillard C, Bourgain JL, Bouroche G, Desplanque L, Devys JM, et al. Guidelines on 
muscle relaxants and reversal in anaesthesia. Anaesth Crit Care Pain Med. 2020 Feb 
1;39(1):125–42.  

LARINGOCOL Non-inferiority Clinical Trial 
Protocol IN29-2025 Original 1.0 
11 September 2025 
62 
 
75. Mosier JM, Sakles JC, Stolz U, Hypes CD, Chopra H, Malo J, et al. Neuromuscular Blockade 
Improves First-Attempt Success for Intubation in the Intensive Care Unit. A Propensity Matched 
Analysis. Ann Am Thorac Soc. 2015 May;12(5):734–41.  
76. Informe Belmont: Principios éticos y directrices para la protección de sujetos humanos de 
investigación. Dep Health Educ Welf. 1979 Apr;44(76):23192–23197.  
77. Asociación Médica Mundial. Declaración de Helsinki de la AMM – Principios éticos para las 
investigaciones médicas con participantes humanos. Adoptada en 1964 y enmendada por 
última vez en la 75.a. Asamblea General, Helsinki (Finlandia); 2024.  
78. Council for International Organizations of Medical Sciences (CIOMS). International Ethical 
Guidelines for Health-related Research involving Humans [Internet]. Council for International 
Organizations of Medical Sciences (CIOMS); 2016 [cited 2025 Aug 20]. Available from: 
https://cioms.ch/publications/product/international-ethical-guidelines-for-health-related-
research-involving-humans/ 
79. Colombia. Ministerio de Salud. Resolución No. 8430 de 1993, por la cual se establecen las 
normas científicas, técnicas y administrativas para la investigación en salud. 1993 Oct 
4;(8430):577.  
80. Decreto 1377 de 2013 - Gestor Normativo [Internet]. [cited 2025 Aug 20]. Available from: 
https://www.funcionpublica.gov.co/eva/gestornormativo/norma.php?i=53646 
81. Emanuel EJ, Wendler D, Grady C. What Makes Clinical Research Ethical? JAMA. 2000 May 
24;283(20):2701–11.  
82. Trent SA, Driver BE, Prekker ME, Barnes CR, Brewer JM, Doerschug KC, et al. Defining 
Successful Intubation on the First Attempt Using Both Laryngoscope and Endotracheal Tube 
Insertions: A Secondary Analysis of Clinical Trial Data. Ann Emerg Med. 2023 Oct;82(4):432–7.