Role of Doxycycline in Chronic Rhinosinusitis With Nasal Polyps

Sponsor

Assiut University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05157412

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

To evaluate the efficacy of Doxycycline as an adjunct to systemic steroids in the treatment of chronic rhinosinusitis with nasal polyps

Condition or Disease	Intervention/Treatment	Phase
Nasal Polyps Chronic Rhinosinusitis With Nasal Polyps	Drug: Doxycycline 100 mg Oral Tablet Drug: Prednisolone 20 mg	Phase 3

Detailed Description

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease of the nose and paranasal sinuses characterized by mucosal thickening and polyp formation. The prevalence of CRSwNP in the general population ranges between 1 and 4%. It mostly affects adult individuals. The treatment of CRSwNP can include the use of steroids, antibiotics, saline nasal spray, mucolytics, topical/systemic decongestants, topical anticholinergics, anti-leukotrienes or receptor blockers, and antihistamines. Steroids have a multitude of effects, including inhibition of cytokine synthesis, reduction of the number of eosinophils and activated eosinophils, anti-oedema effects and reduction of transudation. Topical corticosteroid therapy is not effective in all patients, leading to the use of systemic glucocorticosteroids and/or sinus surgery to control the disease. As a new approach, antibiotics are being used to treat CRSwNP particularly in patients with disease exacerbated by the Staphylococcus aureus enterotoxin. Antibiotics with anti- inflammatory effects can be used to treat patients with chronic rhinosinusitis without polyps, which might be the precursor to CRSwNP. Long-term treatment with these drugs, in selected cases, may be effective when corticosteroids fail. Doxycycline has dual action: it has well described, broad-spectrum antibacterial activity against S aureus as well as anti-inflammatory properties. It appears to be effective in treatment of several chronic inflammatory airway diseases.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Role of Doxycycline in the Management of Patients With Chronic Rhinosinusitis With Nasal Polyps

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Steroids + Doxycycline Systemic Prednisolone in decreasing doses (40 mg/d on days 1-7, 20 mg/d on days 8-14, and 10 mg/d on days 15-21) along with Doxycycline (200 mg as a loading dose on the 1st day, followed by 100 mg once daily one hour before meal as a maintenance dose) for 3 weeks.	Drug: Doxycycline 100 mg Oral Tablet Oral Doxycycline will be added to prednisolone as a comparison to using prednisolone as a sole therapy for the treatment of nasal polyps associated with chronic rhinosinusitis Other Names: doxycycline Drug: Prednisolone 20 mg Prednisolone will be used in both arms as a sole therapy in one and together with doxycycline in the other Other Names: prednisolone
Active Comparator: Steroids Only Systemic Prednisolone in decreasing doses (40 mg/d on days 1-7, 20 mg/d on days 8-14, and 10 mg/d on days 15-21) for 3 weeks.	Drug: Prednisolone 20 mg Prednisolone will be used in both arms as a sole therapy in one and together with doxycycline in the other Other Names: prednisolone

Arm

Intervention/Treatment

Experimental: Steroids + Doxycycline

Systemic Prednisolone in decreasing doses (40 mg/d on days 1-7, 20 mg/d on days 8-14, and 10 mg/d on days 15-21) along with Doxycycline (200 mg as a loading dose on the 1st day, followed by 100 mg once daily one hour before meal as a maintenance dose) for 3 weeks.

Drug: Doxycycline 100 mg Oral Tablet

Oral Doxycycline will be added to prednisolone as a comparison to using prednisolone as a sole therapy for the treatment of nasal polyps associated with chronic rhinosinusitis

Other Names:

doxycycline

Drug: Prednisolone 20 mg

Prednisolone will be used in both arms as a sole therapy in one and together with doxycycline in the other

Other Names:

prednisolone

Active Comparator: Steroids Only

Systemic Prednisolone in decreasing doses (40 mg/d on days 1-7, 20 mg/d on days 8-14, and 10 mg/d on days 15-21) for 3 weeks.

Drug: Prednisolone 20 mg

Prednisolone will be used in both arms as a sole therapy in one and together with doxycycline in the other

Other Names:

prednisolone

Outcome Measures

Primary Outcome Measures

Polyp Size Score by Nasal Endoscopy [after 12 weeks from the start of treatment]
Every patient will undergo nasal endoscopy at the initial visit and every follow-up visit using a modified Lildholdt scoring system and given scores from 0 to 4. The total nasal polyp score is the sum of the scores from the right and left nostrils. 0 = No polyps. = Small polyps in the middle meatus not reaching below the inferior border of the middle concha. = Polyps reaching below the lower boarder of the middle turbinate. = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha. = Large polyps causing almost complete obstruction of the inferior meatus.
Radiological Evaluation [after 12 weeks from the start of treatment]
Multislice computed tomography scan of the nose and paranasal sinuses will be done before starting the treatment and at the end of the follow-up period (12 weeks) using the Lund-Mackay (LMK) scoring system where each sinus (maxillary, anterior ethmoidal, posterior ethmoidal, frontal, sphenoidal) is scored for opacification (0, no opacity; 1, partial opacity; 2, total opacity), and the osteo-meatal complex is scored 0 (no obstruction) or 2 (obstruction). The unilateral score goes from 0 to 12 whereas the bilateral score goes from 0 to 24

Secondary Outcome Measures

Laboratory Measures [after 12 weeks from the start of treatment]
Complete Blood count specifically the eosinophilic count (both relative and absolute) will be documented at the initial visit and at the end of treatment. Values of each group will be compared to each other.
Symptomatology [after 12 weeks from the start of treatment]
Using a questionnaire, all subjects will be asked to evaluate five symptoms (nasal obstruction, Rhinorrhea, postnasal discharge, hyposmia and facial pain) from 0 to 4. 0 = no symptoms = mild symptoms = moderate symptoms = severe symptoms = very severe symptoms (intolerable) This will be assessed at the screening visit and follow-up visits at 3, 8 and 12 weeks as a sum of the five individual symptoms of a total score of 20.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1- Adult patients (aged 18 and over) with bilateral nasal polyps confirmed by nasal endoscopy and CT scan.

Exclusion Criteria:

CRS without nasal polyps.
Unilateral nasal polyps.
Pregnant and lactating women.
Patients younger than 18 years old.
Subjects with known allergic reaction to steroids or tetracyclines, hypertension, diabetes (type 1 and 2), glaucoma, tuberculosis, herpes infection are excluded.
If any major complications to the drugs in use appeared in process.