Clinical Trial to Evaluate the Efficacy and Safety of SUBMO® as a Submucosal Injection Agent in Endoscopic Resection of Superficial Gastrointestinal Lesions.

Randomized Clinical Trial to Evaluate the Efficacy and Safety of the Use of a Medical Device (SUBMO®) for Submucosal Injection in Endoscopic Resection Techniques of Superficial Gastrointestinal Lesions.

The SUBMO-PIC01-2025 study evaluates whether SUBMO®, a submucosal injection hydrogel composed of high-molecular weight hyaluronic acid and methylene blue, is as effective and safe as normal saline for endoscopic resection of superficial colorectal lesions larger than 10 mm. Its primary aim is to determine non-inferiority in complete resection rates, whether en bloc or fragmented, and to assess safety through the systematic identification of serious adverse events. Secondary aims include analysing the total volume of product needed, the number of injections required, the maintenance of the submucosal cushion, the duration of the procedure, the ease of resection, the subjective evaluation of endoscopists, and the appearance of additional adverse events related to the intervention such as intraprocedural bleeding, fever, significant post-procedure pain, post-coagulation syndrome or immediate or delayed perforation.

Eligible participants are adults aged 18 or older with a confirmed colorectal lesion greater than 10 mm that is technically resectable using EMR or ESD, who are capable and willing to follow the study procedures and who have signed informed consent prior to any protocol-specific action. Exclusion criteria include severe comorbidities corresponding to ASA IV or V unless specifically authorised by anaesthesia, coagulopathies that prevent endoscopic resection, endoscopic suspicion of invasive cancer, any condition deemed by investigators to compromise safety or adherence, known allergy to hyaluronic acid, methylene blue or excipients, contraindications to colonoscopy or sedation, participation in another clinical investigation within the previous 30 days, and pregnancy or breastfeeding. Participants may be withdrawn due to voluntary consent withdrawal, safety concerns, protocol deviations that affect data integrity or patient safety, loss to follow-up or pregnancy discovered during the study.

The main efficacy variable is the technical success of resection as judged immediately by the endoscopist, while the main safety variable is the incidence of serious adverse events and their causal relationship with the investigational product. Exploratory variables include baseline demographics such as age, sex, ethnic origin and body mass index, anticoagulant or antiplatelet medication, and comorbidities including endoscopic history, obesity, hypertension, cardiovascular disease, haematologic disorders such as von Willebrand disease or haemophilia, and chronic liver disease. Baseline variables also include ASA classification and lifestyle habits. Polyp-related variables include size, number, anatomical location in the colon or rectum, LST subtype and JNET classification. Resection-related variables capture the technique used (EMR or ESD), whether the resection is en bloc or piecemeal, the number of fragments for calculating the Sydney Resection Quotient, the DMI score and any closure technique or complications. Treatment-related variables include total and per-surface area injection volume, number of submucosal injections needed, macroscopic evaluation of cushion maintenance, total procedure time, ease of resection using a visual analogue scale from 0 to 100, a usability questionnaire completed by the endoscopists and a detailed record of all adverse events including bleeding, fever, pain, post-coagulation syndrome and perforation.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Polyps
• Intervention / Treatment: Device: SUBMO® Submucosal Injection; Device: Normal Saline (0.9% Sodium Chloride) with Surface Dye Injection

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Josune Torrecilla; Phone Number: +34945561134; Email: jtorrecilla@imasmed.com

Study Locations

• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08026
      • Hospital Unversitario de la Santa Creu i Sant Pau
      • Contact: Jorge Gordillo, Ábalos; Phone Number: 935 565 920; Email: JGordillo@santpau.cat
    • Manresa, Barcelona, Spain, 08243
      • Hospital Althaia
      • Contact: Marco Antonio Álvarez, Dr; Phone Number: 938 759 300; Email: marcoalgo@gmail.com
  • Bizkaia
    • Bilbao, Bizkaia, Spain, 48013
      • Hospital Universitario Basurto
      • Contact: Ángel Calderón, Dr; Phone Number: 944 00 60 00; Email: angeljose.calderongarcia@osakidetza.eus
    • Bilbao, Bizkaia, Spain, 48903
      • Hospital De Cruces
      • Contact: David Coto, Dr; Phone Number: 946 00 60 00; Email: david.cotougarte@osakidetza.eus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects >18 years old.
• Presence of a colorectal lesion larger than 10 mm, confirmed through colonoscopy.
• The lesion must be considered technically resectable using either Endoscopic Mucosal Resection (RME) or Endoscopic Submucosal Dissection (DSE).
• The participant must be willing and able to comply with all required study visits and procedures, according to the protocol.
• The participant must understand, sign, and date the written informed consent form before undergoing any study-specific procedures.

Exclusion Criteria:

• Severe comorbidities according to clinical judgment, including patients classified as ASA IV or ASA V, except those ASA IV cases explicitly approved as clinically safe by the center's Anesthesiology Service (using the ASA anesthetic classification).
• Patients presenting some coagulopathy that prevents safe endoscopic resection.
• Lesions that are suspicious endoscopic invasive cancer.
• Any medical condition that, in the investigator's opinion, could compromise patient safety or protocol adherence.
• Known allergy or hypersensitivity to any component of the investigational product, including hyaluronic acid, methylene blue, or any excipients.
• Contraindications to colonoscopy or to the administration of sedation/anesthesia.
• Current participation in another clinical investigation with an investigational product, or participation in any clinical study (with tested or untested products) within the previous 30 days prior to randomization.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SUBMO® Submucosal Injection; SUBMO® is a sterile, pyrogen-free hydrogel composed of high-molecular-weight sodium hyaluronate combined with methylene blue and buffered salts in an isotonic, physiological-pH solution. It is designed to act as a submucosal filler, creating a stable and long-lasting elevation between mucosal and muscular layers. The formulation provides structural support due to its viscosity and enhances visualization through integrated methylene blue. SUBMO® is supplied in 10 mL prefilled borosilicate glass syringes and is classified as a Class III medical device without CE marking.	Device: SUBMO® Submucosal Injection; Participants randomized to this arm undergo endoscopic resection (EMR or ESD) in which the submucosal injection is performed using SUBMO®, a high-viscosity hydrogel composed of high-molecular-weight hyaluronic acid and methylene blue. SUBMO® is administered through a standard injection needle to create and maintain a stable submucosal cushion that facilitates safe and complete resection of colorectal lesions. Its integrated dye enhances visualization of the submucosal layer. All other aspects of the procedure follow routine clinical practice.
Active Comparator: Normal Saline (0.9% Sodium Chloride) with Surface Dye Injection; The control product is 0.9% sodium chloride solution (normal saline), used as a standard, low-viscosity submucosal injection fluid. To ensure visualization comparable to the experimental product, a non-infused surface dye such as methylene blue or indigo carmine is added according to routine hospital practice. Saline provides a short-lasting mucosal lift and does not contain structural polymers or integrated colorants. It represents the current reference solution widely used for submucosal elevation.	Device: Normal Saline (0.9% Sodium Chloride) with Surface Dye Injection; Participants in this arm undergo endoscopic resection using normal saline as the submucosal injection solution, combined with surface dye staining (methylene blue or indigo carmine) prepared as customary in hospital practice, ensuring visibility equivalent to that of the experimental product. Saline is injected to raise the mucosa and allow resection, following standard EMR or ESD clinical techniques. This arm represents the current standard of care for submucosal injection in colorectal lesion resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resection (RME / ESD) Technical Success	Resection technical success represents the immediate procedural success of the endoscopist in achieving a complete resection of the target lesion. Assessment is based on the endoscopist's expert judgement of whether the entire lesion has been removed, following either EMR (Endoscopic Mucosal Resection) or ESD (Endoscopic Submucosal Dissection). The result is recorded dichotomously (success / no success). At the end of the study, this outcome will be expressed as the percentage of patients in each treatment arm who achieved complete resection.	Immediatly after procedure (day 0)
Incidence and Characterisation of Serious Adverse Events (SAEs)	This is the primary safety outcome and includes all serious adverse events occurring from the moment a patient receives the investigational or control product until the end of follow-up.	Throughout the study (from day 0 to 1 month)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total size of the lesion (mm)	Measurement of the total size of the lesion (the largest lesion will be used as reference in the measurement) (measured in millimeters).	During intervention (day 0)
Number of lesions (>10 mm)	Measurement of the number of lesions larger than 10 mm.	During intervention (day 0)
Anatomical location of the lesion	Description of the anatomical location within the colon or rectum (right colon, transverse colon, left colon, or rectum).	During intervention (day 0)
LST (Lateral Spreading Tumor) classification	Classification of the polyps that spread laterally across de mucosa, it predicts the risk of the submucosa infiltration. The classification will be divided into two groups: Granular polyps (LST-G) and Non-Granular polyps (LST-NG)	During intervention (day 0)
JNET (Japanese NBI Expert Team) classification	Classification that divides NICE 2 lesions into 2 groups: 2A (low grade adenomas) and 2B (high grade adenomas, incorporating the cancers that infiltrate the submucosa superficially)	During intervention (day 0)
Resection Technique	Resection technique used (EMR vs. ESD). Fragmentation data are used to calculate the Sydney Resection Quotient, a metric reflecting resection efficiency and difficulty (lesion size divided by number of fragments).	During intervention (Day 0)
Analysis of lesion removal (single piece removal vs. multiple fragments removal)	Analysis of the outcome of the resection measure as wether the lesion was removed in a single piece or multiple fragments. Sydney Resection Quotient is calculated for the multiple fragment removal, a metric reflecting resection efficiency and difficulty (lesion size divided by number of fragments).	During intervention (Day 0)
Number of Fragments collected	Analysis of the number of fragments collected when piecemeal resection occurs. Fragmentation data are used to calculate the Sydney Resection Quotient, a metric reflecting resection efficiency and difficulty (lesion size divided by number of fragments).	During intervention (Day 0)
Sydney Deep Mural Injury Score (DMI)	Analysis of the Sydney Deep Mural Injury (DMI) score (0 to IV points), which assesses the depth of tissue injury (0-Normal defect; IV-actual hole with a white cautery ring).	During intervention (Day 0)
Closure Techniques vs. Hemostatic measures	Documentation of whether closure techniques or hemostatic measures were applied (such as clipping, coagulation, or other methods).	During intervention (Day 0)
Intra-procedural complications	Data on intra-procedural complications, whether minor or significant, are recorded.	During intervention (Day 0)

Collaborators and Investigators

• Sponsor: i+Med S.Coop.
• Collaborators: Hospital Sant Joan de Deu; Hospital de Cruces; Fundació Institut de Recerca del Hospital Santa Creu i Sant Pau; Hospital Universitario Basurto
• Investigators: Principal Investigator: Angel Calderón, Dr, Hospital Universitario Basurto

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Submucosal injection; endoscopic resection; hyaluronic acid hydrogel
• Other Study ID Numbers: SUBMO-PIC01-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No