search
Back to results

4"S" - Seasonal Symptoms Suppression Study (4"S")

Primary Purpose

Seasonal Allergic Rhinitis

Status
Unknown status
Phase
Phase 4
Locations
Bulgaria
Study Type
Interventional
Intervention
Xylometazoline - intranasal application
Azelastine - intranasal application
Mometasone furoate - intranasal application
Hydroxyl-propyl-methyl cellulose powder - intranasal application
Placebo - Lactose powder
Bilastine 20 mg
Prednisolone 5 mg
Sponsored by
Association Asthma, Bulgaria
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Seasonal Allergic Rhinitis focused on measuring Pollenosis, Congestion, Mucoadhesive Treatment, Nasal Decongestant, Nasal Antihistamine, Nasal Corticosteroid

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients
  • Age ≥ 18 and ≤ 55 years
  • Personal history of rhinitis during the pollen season
  • Moderately severe / severe seasonal allergic rhinitis (grass)
  • Positive skin prick test for grass/cereals

Exclusion Criteria:

  • Subjects with arterial hypertension, arrhythmia or evidence of heart ischemia
  • Subjects with other serious chronic comorbidities and bad therapeutic control
  • Subjects with nasal polyposis
  • Any contraindications for xylometazoline
  • Any contraindications for HPMC
  • Any contraindications for azelastine
  • Any contraindications for bilastine
  • Any contraindications for mometasone
  • Any contraindications for prednisolone
  • Subjects unable to give informed consent
  • Pregnant or lactating women

Sites / Locations

  • Medical University Sofia, University Hospital "Alexandrovska", Clinic of Allergy and Asthma

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Other

Arm Label

Group HPMC

Group Placebo

Group Immunotherapy

Arm Description

Hydroxyl-propyl-methyl-cellulose (HPMC) powder added immediately after other intranasal treatment options

Lactose powder (placebo) added immediately after other intranasal treatment options

Immunotherapy group with grass allergens sublingually (Staloral #688) and rescue medication

Outcomes

Primary Outcome Measures

Combined Sypmtom and Medication Score
The primary outcome will be comparison of total combined symptoms and medication scores (TCSMS) collected from patients' diaries for a fixed period during the pollen season

Secondary Outcome Measures

Drug Specific Combined Sypmtom and Medication Score
Drug specific combined symptoms and medication scores (DsCSMS) will be calculated for each rescue medication and compared between the 3 arms of the trial.
Visual Analogue Scale
Visual analogue scale (VAS) scores (Scores range from 0 [no symptoms] to 10 [worst possible symptoms]) at each visit and compared between groups.

Full Information

First Posted
July 17, 2015
Last Updated
September 21, 2015
Sponsor
Association Asthma, Bulgaria
Collaborators
Nasaleze
search

1. Study Identification

Unique Protocol Identification Number
NCT02557269
Brief Title
4"S" - Seasonal Symptoms Suppression Study
Acronym
4"S"
Official Title
Real Life Proof-of-Concept Study to Assess the Effect of Methylcellulose as add-on "Seal" to the In-season Pharmacologic Rescue Treatment in Subjects With Allergic Rhinitis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Unknown status
Study Start Date
May 2015 (undefined)
Primary Completion Date
October 2015 (Anticipated)
Study Completion Date
December 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Association Asthma, Bulgaria
Collaborators
Nasaleze

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
ASIT naïve patients sensitized to grass pollens will be recruited for the study. All of them will be instructed to treat bothersome in-season symptoms when they appear (on as needed, pro re nata basis) with rescue medication. They will be given 5 different options and will be informed about the effects of each of them in order to make their optimal choice for different symptoms and their combination: local decongestant (xylomethazoline, when congestion is leading), local antihistamine (azelastine, when itching, sneezing and rhinorhea a predominant), nasal corticosteroid (momethasone, when all nasal symptoms are pressing and no adequate relief is obtained form the other 2 local treatments), oral antihistamine (bilastine, when itching and sneezing persist despite the local treatments) and oral corticosteroid (prednisolone, when any or all symptoms become unbearable despite the other suggested treatments). Patients who are reluctant to use immunotherapy or who are too late to initiate it will be randomized to be treated with the listed medications on as needed basis, the nasally applied formulations will be followed by either HPMC to prolong and enhance their effect (Group HPMC) or placebo (lactose powder) (Group Placebo) to serve as control. Patients indicated and willing to carry out ASIT will be treated according to the standard protocol with grass allergens sublingually (Staloral #688) and will receive rescue medication (Group Immunotherapy).
Detailed Description
Rationale. Assessment and follow up of specifically sensitized subjects with allergic rhinitis during the pollen season is traditionally based on symptom scores. Accounting for the use of rescue medication on top of symptom scores provides another dimension to the overall clinical characterization of the patients. Thus, using "combined symptom and medication scores" (CSMS) allows thorough characterization of the disease course. Guidelines recommend that CSMS are used for assessment of the effect of allergen specific immunotherapy in subjects with allergic rhinitis. Different allergic rhinitis management strategies can be evaluated and compared by means of CSMS. In the update of the ARIA guidelines of 2010, 24 recommendations have been made in relation to pharmacologic treatment. Special position paper has been devoted to severe chronic upper airway disease (SCUAD), the treatment for which has been earmarked as unmet need. Consequently, a standardized and universally recognized rescue treatment strategy does not exist. The most common approach for handling nasal complaints in real life consists in using rescue medication for symptoms whenever they appear. This is certainly the case when symptoms appear for the first time ever, or when patients do not want to resort to allergen specific immunotherapy (ASIT) and / or regular oral antihistamine treatment for financial reasons or personal beliefs. Under these circumstances, a long list of pharmacological choices for local or systemic application is possible including antihistamines, corticosteroids, leukotriene antagonists, cromones and antimuscarinic drugs. Formulations for local application in the nose appeal to patients with their ease of use and immediate relief. They comprise a variety of generic drugs: decongestants, antihistamines, corticosteroids and antimuscarinics. The fact that they are not ingested makes them first choice for people reluctant to take oral medications. In many cases it is possible to control the symptoms of allergic rhinitis with these formulations used per se or as adjunct rescue medication in the course of ASIT. The question stays whether the effectiveness of nasally applied drugs can further be improved. Despite the good rationale for their mechanism of action, their efficacy is diminished by the cleaning mechanisms of the nose, rhinorrhea in particular. Slowing down of the clearance of the nasal mucosa and prolonging the contact time with the nasal mucosa would enhance their pharmaceutical effects. The investigators have demonstrated by objectively measuring nasal flow rates that "sealing" in place locally applied oxymetazoline in subjects with persistent allergic rhinitis by means of commercially available hydroxyl-propyl-methyl-cellulose (HPMC) significantly enhances the resulting decongestion and that this effect is augmented over a time span of 2 weeks without noticeable tachyphylaxis or adverse events. The investigators set the aim to investigate whether this beneficial effect of HPMC translates into clinical benefits in a real life clinical trial for other available drug preparations for nasal delivery. Study design. ASIT naïve patients sensitized to grass pollens will be recruited for the study. All of the patients will be instructed to treat bothersome in-season symptoms when they appear (on as needed, pro re nata basis) with rescue medication. The patients will be given 5 different options and will be informed about the effects of each of them in order to make their optimal choice for different symptoms and their combination: local decongestant (xylomethazoline, when congestion is leading), local antihistamine (azelastine, when itching, sneezing and rhinorhea a predominant), nasal corticosteroid (momethasone, when all nasal symptoms are pressing and no adequate relief is obtained form the other 2 local treatments), oral antihistamine (bilastine, when itching and sneezing persist despite the local treatments) and oral corticosteroid (prednisolone, when any or all symptoms become unbearable despite the other suggested treatments). Patients who are reluctant to use immunotherapy or who are too late to initiate it will be randomized to be treated with the listed medications on as needed basis, the nasally applied formulations will be followed by either HPMC to prolong and enhance their effect (Group HPMC) or placebo (lactose powder) (Group Placebo) to serve as control. Patients indicated and willing to carry out ASIT will be treated according to the standard protocol with grass allergens sublingually (Staloral #688) and will receive rescue medication (Group Immunotherapy).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Seasonal Allergic Rhinitis
Keywords
Pollenosis, Congestion, Mucoadhesive Treatment, Nasal Decongestant, Nasal Antihistamine, Nasal Corticosteroid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group HPMC
Arm Type
Active Comparator
Arm Description
Hydroxyl-propyl-methyl-cellulose (HPMC) powder added immediately after other intranasal treatment options
Arm Title
Group Placebo
Arm Type
Placebo Comparator
Arm Description
Lactose powder (placebo) added immediately after other intranasal treatment options
Arm Title
Group Immunotherapy
Arm Type
Other
Arm Description
Immunotherapy group with grass allergens sublingually (Staloral #688) and rescue medication
Intervention Type
Drug
Intervention Name(s)
Xylometazoline - intranasal application
Intervention Description
Applied as needed up to 5 consecutive days when prominent congestion
Intervention Type
Drug
Intervention Name(s)
Azelastine - intranasal application
Other Intervention Name(s)
Allergodil
Intervention Description
Applied as needed when prominent symptom is rhinorrhea
Intervention Type
Drug
Intervention Name(s)
Mometasone furoate - intranasal application
Other Intervention Name(s)
Nasonex
Intervention Description
Applied once daily (2 puffs) when no satisfactory therapeutic control from other intranasal treatment
Intervention Type
Drug
Intervention Name(s)
Hydroxyl-propyl-methyl cellulose powder - intranasal application
Other Intervention Name(s)
Nasaleze
Intervention Description
Applied intranasally immediately after every application other intranasal formulation
Intervention Type
Other
Intervention Name(s)
Placebo - Lactose powder
Intervention Description
Applied intranasally immediately after every application other intranasal formulation
Intervention Type
Drug
Intervention Name(s)
Bilastine 20 mg
Other Intervention Name(s)
Fortecal
Intervention Description
1 tablet per os - as needed
Intervention Type
Drug
Intervention Name(s)
Prednisolone 5 mg
Intervention Description
Per os - if needed (only in case of broncial obstruction)
Primary Outcome Measure Information:
Title
Combined Sypmtom and Medication Score
Description
The primary outcome will be comparison of total combined symptoms and medication scores (TCSMS) collected from patients' diaries for a fixed period during the pollen season
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Drug Specific Combined Sypmtom and Medication Score
Description
Drug specific combined symptoms and medication scores (DsCSMS) will be calculated for each rescue medication and compared between the 3 arms of the trial.
Time Frame
Up to 6 months
Title
Visual Analogue Scale
Description
Visual analogue scale (VAS) scores (Scores range from 0 [no symptoms] to 10 [worst possible symptoms]) at each visit and compared between groups.
Time Frame
Up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients Age ≥ 18 and ≤ 55 years Personal history of rhinitis during the pollen season Moderately severe / severe seasonal allergic rhinitis (grass) Positive skin prick test for grass/cereals Exclusion Criteria: Subjects with arterial hypertension, arrhythmia or evidence of heart ischemia Subjects with other serious chronic comorbidities and bad therapeutic control Subjects with nasal polyposis Any contraindications for xylometazoline Any contraindications for HPMC Any contraindications for azelastine Any contraindications for bilastine Any contraindications for mometasone Any contraindications for prednisolone Subjects unable to give informed consent Pregnant or lactating women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Todor A Popov, MD, PhD
Organizational Affiliation
Medical University of Sofia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University Sofia, University Hospital "Alexandrovska", Clinic of Allergy and Asthma
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria

12. IPD Sharing Statement

Citations:
PubMed Identifier
24761804
Citation
Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, Durham SR, Jacobsen L, Malling HJ, Mosges R, Papadopoulos NG, Rak S, Rodriguez del Rio P, Valovirta E, Wahn U, Calderon MA; European Academy of Allergy and Clinical Immunology. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy. 2014 Jul;69(7):854-67. doi: 10.1111/all.12383. Epub 2014 Apr 25.
Results Reference
background
PubMed Identifier
24773171
Citation
Calderon MA, Bernstein DI, Blaiss M, Andersen JS, Nolte H. A comparative analysis of symptom and medication scoring methods used in clinical trials of sublingual immunotherapy for seasonal allergic rhinitis. Clin Exp Allergy. 2014 Oct;44(10):1228-39. doi: 10.1111/cea.12331.
Results Reference
background
PubMed Identifier
20816182
Citation
Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schunemann HJ; Global Allergy and Asthma European Network; Grading of Recommendations Assessment, Development and Evaluation Working Group. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010 Sep;126(3):466-76. doi: 10.1016/j.jaci.2010.06.047.
Results Reference
background
PubMed Identifier
19660803
Citation
Bousquet J, Bachert C, Canonica GW, Casale TB, Cruz AA, Lockey RJ, Zuberbier T; Extended Global Allergy and Asthma European Network, World Allergy Organization and Allergic Rhinitis and its Impact on Asthma Study Group. Unmet needs in severe chronic upper airway disease (SCUAD). J Allergy Clin Immunol. 2009 Sep;124(3):428-33. doi: 10.1016/j.jaci.2009.06.027. Epub 2009 Aug 5.
Results Reference
background
PubMed Identifier
26133030
Citation
Valerieva A, Popov TA, Staevska M, Kralimarkova T, Petkova E, Valerieva E, Mustakov T, Lazarova T, Dimitrov V, Church MK. Effect of micronized cellulose powder on the efficacy of topical oxymetazoline in allergic rhinitis. Allergy Asthma Proc. 2015 Nov-Dec;36(6):e134-9. doi: 10.2500/aap.2015.36.3879. Epub 2015 Jun 29.
Results Reference
background

Learn more about this trial

4"S" - Seasonal Symptoms Suppression Study

We'll reach out to this number within 24 hrs