Effectiveness of Endonasal Polymeric Implant for Chronic Rhinosinusitis

Effectiveness of Endonasal Polymeric Implant in the Treatment of Chronic Eosinophilic and Central Compartment Rhinosinusitis: a Randomized Controlled Trial

Objective: The objective of this study is to evaluate a steroid-embedded Terpolymers polymer implant of L-lactide and trimethynele carbonate (TCM) at the level of disease control in patients with eosinophilic and central compartment chronic rhinosinusitis (CRS) after placement of the endonasal device, compared to a control group (placebo). The secondary objectives of this study are to assess comfort, perception of improvement and satisfaction, as well as adverse events.

Methods: A randomized controlled trial will be carried out, with a blinded participant, therapist and evaluator. Patients over 18 years of age, with chronic rhinosinusitis (CRS) who have already undergone endoscopic sinus surgery (CENS), but who do not have the disease under control and, therefore, with an indication for a new CENS, will be selected. Participants will come from the otorhinolaryngology outpatient clinic of the academic and public service of the University of São Paulo - USP. Eligible patients will receive either the Terpolymers L-lactide and trimethynele carbonate (TCM) polymer implant placement or the placebo polymer. The primary outcome will be the control of the symptoms of chronic uncontrolled rhinosinusitis that will be evaluated through the NOSE Questionnaire, a nasal endoscopic evaluation based on the Lund-Kennedy criteria and the SNOT-22 Questionnaire. The sample size calculation was performed based on a difference between the intervention and placebo groups of 30% for cases that achieved disease control, resulting in a sample of 36 participants (18 in each group). Data will be analyzed using mixed linear models.

Study Overview

• Status: Recruiting
• Conditions: Rhinosinusitis Chronic
• Intervention / Treatment: Other: Placebo; Drug: Corticosteroid Topical

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil
      • Recruiting
      • Luiz Eduardo Flório Junior
      • Contact: Luiz Eduardo Flório Junior, MD; Phone Number: 55 15 98108-0412; Email: luiz-florio@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Patients with chronic rhinosinusitis undergoing endoscopic sinus surgery, but who do not have the disease under control. The uncontrolled disease and its respective classification regarding the degree of the disease will be carried out through 3 assessments: 1) Nose Obstruction Symptom Evaluation Questionnaire (NOSE) validated version in Portuguese; 2) nasal endoscopic evaluation; and, 3) Sino Nasal Outcome Test Questionnaire (SNOT-22). Through the NOSE questionnaire, the patient's disease will be classified as "Controlled", "Partially Controlled" or "Uncontrolled (Uncontrolled)". Any variation in the endoscopic evaluation score based on the Lund-Kennedy Criteria will be considered an alteration. And for the SNOT-22 Questionnaire, changes will be considered when the total score varies by at least 11 points. Patients who present these 3 alterations will be considered to have the 'uncontrolled disease' and, therefore, will be eligible for the study.

Exclusion Criteria:

• Patients with malformations, trauma and/or tumors in the nasal and paranasal sinuses will be excluded;
• Patients with a history of recent nasal surgery up to 6 months previously, with glaucoma and cataracts.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-lactide and trimethynele carbonate Terpolymers polymer implant; The polymer implant will be placed in the ethmoidal region, at the same time that the nasal endoscopic examination will be performed. The polymer in this study is biocompatible. The polymers will be made in the biomaterials laboratory located at the Pontifical Catholic University of São Paulo (PUC-SP), located in the city of Sorocaba-SP. Polymers will be provided free of charge for the study.	Drug: Corticosteroid Topical; The L-lactide and trimethynele carbonate (TCM) Terpolymers polymer implant will be placed in the ethmoidal region, at the same time that the nasal endoscopic examination will be performed.
Placebo Comparator: Placebo polymer implant	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal Obstruction	Nasal Obstruction, Sistemic medication and Endoscopy (NOSE) questionnaire. NOSE is a method of evaluating the clinical control of chronic rhinosinusitis and is based on the evaluation of three aspects: nasal obstruction, nasal endoscopy and the need for systemic medication (antibiotics or steroids). The NOSE questionnaire consists of five questions concerning subjective assessment of the nasal obstruction within the past month. Each question can be answered usinga 5-point Likert scale from"0"(not a problem) up to"4"(severe problems with breathing). After addition of allitem values and multiplying the raw score with 5, severity of the patient's complaints can be scaled to range from 0 to 100. A score of 0 indicates no obstructivenasal problems and a score of 100 implies severe problems.	Day 15 after intervention
Nasal Endoscopic Evaluation	The nasal endoscopic evaluation will be performed under topical anesthesia, with a rigid endoscope (4mm, 0° and/or 45°; Karl Storz) and its classification will be based on the Lund - Kennedy criteria. For this evaluation, each nostril is examined separately and three possible characteristics may be present, they are: polyps, nasal mucosa edema and/or secretion. For each evaluated characteristic, a score from 0 to 2 is assigned. For the evaluation of polyps, the score is applied as follows: 0=absent; 1=restricted to the middle meatus; and, 2=extension to nasal cavity. For the evaluation of nasal mucosa edema, the score is applied as follows: 0=absent; 1=mild or moderate edema; and 2= polypoid degeneration. For the evaluation of secretion, the score is applied as follows: 0=absent; 1=hyaline secretion; and, 2=mucopurulent or thick secretion.	Day 15 after intervention
Sino Nasal Outcome Test	Sino Nasal Outcome Test (SNOT-22) The SNOT-22 Questionnaire is a modification of the SNOT-20, with 2 additional items on nasal obstruction and problems with smell and taste. The questionnaire assesses 22 items related to nasal symptoms that can impact the patient's personal and social life. Each item can get a score ranging from 0 (least possible problem) to 5 (greatest possible problem). Thus, this questionnaire has a final score that can range from 0 to 110 points. In this study, a significant clinical improvement will be considered when there is at least a variation of 11 points from one assessment to another.23 The validity and reliability of the SNOT-22 have already been previously tested in Portuguese.	Day 15 after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morning serum level of cortisol, albumin and serum globulin	blood test	Day 15 after intervention
Morning serum level of cortisol, albumin and serum globulin	blood test	Day 60 after intervention
ACTH - adrenocorticotropic hormone	blood test	Day 15 and 60 aftern intervention
ACTH - adrenocorticotropic hormone	blood test	Day 15 after intervention
Complete blood count	A complete blood count (CBC) is a blood test used to evaluate your overall health and detect a wide range of disorders, including anemia, infection and leukemia. A complete blood count test measures several components and features of your blood, including: Red blood cells, which carry oxygen White blood cells, which fight infection Hemoglobin, the oxygen-carrying protein in red blood cells Hematocrit, the proportion of red blood cells to the fluid component, or plasma, in your blood Platelets, which help with blood clotting	Day 60 after intervention
total and serum IgE (blood test)	blood test	Day 15 after intervention
total and serum IgE (blood test)	blood test	Day 60 after intervention
Cortisol level in 24-hour urine	urine test	Day 15 after intervention
Cortisol level in 24-hour urine	urine test	Day 60 after intervention
Intraocular pressure profile - IOP	ophthalmologic assessment - fluid overload test and the lens by slit lamp examination	Day 15 after intervention
Intraocular pressure profile - IOP	ophthalmologic assessment - fluid overload test and the lens by slit lamp examination	Day 60 after intervention
Patient comfort	self-reported on an analog scale from 0 to 100, where 0 indicates very uncomfortable and 100 indicates very comfortable	Day 15 after intervention
Patient comfort	self-reported on an analog scale from 0 to 100, where 0 indicates very uncomfortable and 100 indicates very comfortable	Day 60 after intervention
Patient self-reported perception of improvement and satisfaction with the implant	Measured on an analog scale from 0 to 100, where 0 indicates no change in symptoms and dissatisfaction, and 100 indicates resolved symptoms and satisfaction	Day 15 after intervention
Patient self-reported perception of improvement and satisfaction with the implant	Measured on an analog scale from 0 to 100, where 0 indicates no change in symptoms and dissatisfaction, and 100 indicates resolved symptoms and satisfaction	Day 60 after intervention
Adverse events	Adverse events will be measured through changes in blood and urine tests and also on a self-reported basis.	Day 15 after intervention
Adverse events	Adverse events will be measured through changes in blood and urine tests and also on a self-reported basis.	Day 60 after intervention
Nasal Obstruction	Nasal Obstruction, Sistemic medication and Endoscopy (NOSE) questionnaire. NOSE is a method of evaluating the clinical control of chronic rhinosinusitis and is based on the evaluation of three aspects: nasal obstruction, nasal endoscopy and the need for systemic medication (antibiotics or steroids). The NOSE questionnaire consists of five questions concerning subjective assessment of the nasal obstruction within the past month. Each question can be answered usinga 5-point Likert scale from"0"(not a problem) up to"4"(severe problems with breathing). After addition of allitem values and multiplying the raw score with 5, severity of the patient's complaints can be scaled to range from 0 to 100. A score of 0 indicates no obstructivenasal problems and a score of 100 implies severe problems.	Day 45 after intervention
Nasal Obstruction	Nasal Obstruction, Sistemic medication and Endoscopy (NOSE) questionnaire. NOSE is a method of evaluating the clinical control of chronic rhinosinusitis and is based on the evaluation of three aspects: nasal obstruction, nasal endoscopy and the need for systemic medication (antibiotics or steroids). The NOSE questionnaire consists of five questions concerning subjective assessment of the nasal obstruction within the past month. Each question can be answered usinga 5-point Likert scale from"0"(not a problem) up to"4"(severe problems with breathing). After addition of allitem values and multiplying the raw score with 5, severity of the patient's complaints can be scaled to range from 0 to 100. A score of 0 indicates no obstructivenasal problems and a score of 100 implies severe problems.	Day 90 after intervention
Nasal Endoscopic Evaluation	The nasal endoscopic evaluation will be performed under topical anesthesia, with a rigid endoscope (4mm, 0° and/or 45°; Karl Storz) and its classification will be based on the Lund - Kennedy criteria. For this evaluation, each nostril is examined separately and three possible characteristics may be present, they are: polyps, nasal mucosa edema and/or secretion. For each evaluated characteristic, a score from 0 to 2 is assigned. For the evaluation of polyps, the score is applied as follows: 0=absent; 1=restricted to the middle meatus; and, 2=extension to nasal cavity. For the evaluation of nasal mucosa edema, the score is applied as follows: 0=absent; 1=mild or moderate edema; and 2= polypoid degeneration. For the evaluation of secretion, the score is applied as follows: 0=absent; 1=hyaline secretion; and, 2=mucopurulent or thick secretion.	Day 45 after intervention
Nasal Endoscopic Evaluation	The nasal endoscopic evaluation will be performed under topical anesthesia, with a rigid endoscope (4mm, 0° and/or 45°; Karl Storz) and its classification will be based on the Lund - Kennedy criteria. For this evaluation, each nostril is examined separately and three possible characteristics may be present, they are: polyps, nasal mucosa edema and/or secretion. For each evaluated characteristic, a score from 0 to 2 is assigned. For the evaluation of polyps, the score is applied as follows: 0=absent; 1=restricted to the middle meatus; and, 2=extension to nasal cavity. For the evaluation of nasal mucosa edema, the score is applied as follows: 0=absent; 1=mild or moderate edema; and 2= polypoid degeneration. For the evaluation of secretion, the score is applied as follows: 0=absent; 1=hyaline secretion; and, 2=mucopurulent or thick secretion.	Day 90 after intervention
Sino Nasal Outcome Test	Sino Nasal Outcome Test (SNOT-22) The SNOT-22 Questionnaire is a modification of the SNOT-20, with 2 additional items on nasal obstruction and problems with smell and taste. The questionnaire assesses 22 items related to nasal symptoms that can impact the patient's personal and social life. Each item can get a score ranging from 0 (least possible problem) to 5 (greatest possible problem). Thus, this questionnaire has a final score that can range from 0 to 110 points. In this study, a significant clinical improvement will be considered when there is at least a variation of 11 points from one assessment to another.23 The validity and reliability of the SNOT-22 have already been previously tested in Portuguese.	Day 45 after intervention
Sino Nasal Outcome Test	Sino Nasal Outcome Test (SNOT-22) The SNOT-22 Questionnaire is a modification of the SNOT-20, with 2 additional items on nasal obstruction and problems with smell and taste. The questionnaire assesses 22 items related to nasal symptoms that can impact the patient's personal and social life. Each item can get a score ranging from 0 (least possible problem) to 5 (greatest possible problem). Thus, this questionnaire has a final score that can range from 0 to 110 points. In this study, a significant clinical improvement will be considered when there is at least a variation of 11 points from one assessment to another.23 The validity and reliability of the SNOT-22 have already been previously tested in Portuguese.	Day 90 after intervention

Collaborators and Investigators

• Sponsor: University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Anticipated): July 15, 2022
• Study Completion (Anticipated): December 15, 2022

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis
• Other Study ID Numbers: USPStudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No