Roflumilust in Chronic Rhinosinusitis With Nasal Polyposis.

The Potential Therapeutic Effect of Roflumilust (a Selective Phosphodiesterase 4inhibitor) on Chronic Rhinosinusitis With Nasal Polyposis.

The current study will be a pilot study for a randomized controlled trial conducted on 60 patients recruited from the outpatient clinic of the Otorhinolaryngology Department, Menoufia Faculty of Medicine after approval of the institutional review board and taking informed written consent from every patient before participation in the study. The patients of this study will be randomly and equally distributed among case and control groups to compare the effect of Roflumilust administration with the effect of systemic and local corticosteroids on patients with chronic rhinosinusitis with nasal polyposis

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Sinusitis
• Intervention / Treatment: Drug: Roflumilust; Drug: Prednisolone

Detailed Description

The current study will be a pilot study for a randomized controlled trial conducted on 60 patients recruited from the outpatient clinic of the Otorhinolaryngology Department, Menoufia Faculty of Medicine after approval of the institutional review board and taking informed written consent from every patient before participation in the study. The patients of this study will be randomly and equally distributed among case and control groups.

To be included in the study, patients should be more than 18 years old, have chronic rhinosinusitis with nasal polyposis, and have no history of systemic steroid administration over the last three months. History of previous nasal surgery, underlying systemic diseases (like diabetes mellitus, hypertension, or autoimmune diseases), and hypersensitivity to Roflumilust were the exclusion criteria for this study.

Patients of the study will be randomly and equally distributed between case and control groups using block randomization methods using 4 blocks each comprising 4 patients with 6 patterns for every block one of which was selected randomly using random numbers generated by Excel program. The case group will receive a 10 days course of Roflumilust in a dose of 500 mg once daily. The Control group will receive a 10 days course of systemic steroids in the form of oral prednisolone in a dose of 40 mg per day.

Assessment protocol:

Patients of the study will be assessed before and at the end of the treatment protocol with history taking to define the inclusion and exclusion criteria and to assess the burden of nasal symptoms using SNOT-22 scale. Endoscopic examination of the nasal cavity will be performed to confirm the presence of bilateral nasal polyposis and to assess the degree of nasal polyposis using the Lund Kennedy score. Serum IL17 and periostin will be assessed using ELISA technique before and after treatment to assess the anti-inflammatory effects of the drug.

Outcome measures:

Primary outcome measures will include a comparison between the pre and post treatment values of SNOT-22 and Lund Kennedy scores, serum IL17, and serum priostin in both case and control groups. Another outcome measure will be the comparison between the case and control groups regarding the posttreatment and posttreatment values of the previous indices. Secondary outcome measures will include an assessment of the side effects of Roflumilust among the case group.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ahmad M Hamdan, MD; Phone Number: 00201008993175; Email: Ahmed.Hamdan@med.menofia.edu.eg

Study Locations

• Egypt
  • Menoufia
    • Shibīn Al Kawm, Menoufia, Egypt, 32511
      • Menoufia Faculty of Medicine
      • Contact: Ahmad Hamdan, MD; Phone Number: 00201008993175; Email: Ahmed.Hamdan@med.menofia.edu.eg

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:

• chronic rhinosinusitis with nasal polyposis,
• No history of systemic steroid administration over the last three months

Exclusion Criteria:

• History of previous nasal surgery,
• Underlying systemic diseases (like diabetes mellitus, hypertension, or autoimmune diseases),
• Hypersensitivity to Roflumilust

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: Case Group; The case group will receive a 10 days course of Roflumilust in a dose of 500 mg once daily.	Drug: Roflumilust; A selective phosphodiesterase 4 Inhibitor
Active Comparator: Control group; The Control group will receive a 10 days course of systemic steroids in the form of oral prednisolone in a dose of 40 mg per day.	Drug: Prednisolone; Systemic corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison between pretreatment and posttreatment SNOT-22 score in both groups	Post-treatment SNOT-22 scores will be compared with pretreatment scores in both groups	2 weeks after start of treatment
Comparison between pretreatment and posttreatment Lund Kennedy scores in both groups	Post-treatment Lund Kennedy scores will be compared with pretreatment scores in both groups	Two weeks after start of treatment
Comparison between pretreatment and posttreatment Serum periostin levels in both groups	Post-treatment Serum periostin level in pg/ml will be compared with pretreatment levels in both group	Two weeks after start of treatment
Comparison between case and control groups regarding SNOT 22 score	Case and control groups are compared regarding post-treatment SNOT-22 score	Two weeks after start of treatment
Comparison between case and control groups regarding Lund Kennedy score	Case and control groups are compared regarding post-treatment Lund Kennedy score	Two weeks after start of treatment
Comparison between case and control groups regarding serum periostin level	Case and control groups are compared regarding post-treatment serum periostin level in pg/ml	Two weeks after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the side effects of Roflumilust	The side effects of Roflumilust will be assessed among the case group	Two weeks after start of treatment

Collaborators and Investigators

• Sponsor: Menoufia University

Publications and helpful links

General Publications

• Hulse KE, Stevens WW, Tan BK, Schleimer RP. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015 Feb;45(2):328-46. doi: 10.1111/cea.12472.
• Ryu G, Bae JS, Kim JH, Kim EH, Lyu L, Chung YJ, Mo JH. Role of IL-17A in Chronic Rhinosinusitis With Nasal Polyp. Allergy Asthma Immunol Res. 2020 May;12(3):507-522. doi: 10.4168/aair.2020.12.3.507.
• Maxfield AZ, Landegger LD, Brook CD, Lehmann AE, Campbell AP, Bergmark RW, Stankovic KM, Metson R. Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis. Otolaryngol Head Neck Surg. 2018 Jan;158(1):181-186. doi: 10.1177/0194599817737967. Epub 2017 Oct 17.
• Janosova V, Calkovsky V, Pedan H, Behanova E, Hajtman A, Calkovska A. Phosphodiesterase 4 Inhibitors in Allergic Rhinitis/Rhinosinusitis. Front Pharmacol. 2020 Jul 22;11:1135. doi: 10.3389/fphar.2020.01135. eCollection 2020.
• Inagaki N, Miura T, Daikoku M, Nagai H, Koda A. Inhibitory effects of beta-adrenergic stimulants on increased vascular permeability caused by passive cutaneous anaphylaxis, allergic mediators, and mediator releasers in rats. Pharmacology. 1989;39(1):19-27. doi: 10.1159/000138567.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Roflumilust; Chronic Sinusitis with nasal polyposis; Phosphodiesterase inhibitor
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Polyps; Sinusitis; Nasal Polyps; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: 1/2022 ENT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data is available on request from the authors
• IPD Sharing Time Frame: After publication of the study
• IPD Sharing Access Criteria: After approval of the authors on request
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

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