Ignite Creation Date:
2024-05-06 @ 4:47 PM
Last Modification Date:
2024-10-26 @ 2:15 PM
Study NCT ID:
NCT05080322
Status:
RECRUITING
Last Update Posted:
2024-04-04
First Post:
2021-07-27
Brief Title:
Efficacy and Safety of On-demand and Continuous Administration of Nasal Spray in the Treatment of Allergic Rhinitis
Sponsor:
Zheng Liu ENT
Organization:
Tongji Hospital
Study Overview
Official Title:
A Randomized Open-labeled Multicenter Clinical Trial to Compare the Efficacy and Safety of On-demand and Continuous Administration of Nasal Spray in the Treatment of Moderate-to-severe Persistent Allergic Rhinitis
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
WHO recommend to divide AR into 4 subgroups according to the symptom frequency intermittent or persistent and severity mild or moderate-to-severe For the persistent moderate-to-severe AR subgroup the guideline suggests to treat with intranasal corticosteroid INS plus antihistamines AH1 for 2-4 weeks If the symptom is controlled then degrade the treatment usually with INS and maintenance for more than 4 weeks However up to 70 of patients suffering from AR do not follow treatment recommendation they stopped medication when they feel better This behavior always leads to uncontrolled AR which has been identified as a high-risk factor of induction and exacerbation of asthma and chronic rhinosinusitis A recent survey showed that AR patients prefer to an on-demand treatment rather than continuous treatment In general poor adherence is always a considerable issue for all long-term treatments Previous studies have shown that as dosing frequency increases the adherence rate decreases Thus less medication frequency is an important factor to optimize the management of chronic diseases including AR
Intranasal AH1 can relieve AR symptoms including sneezing rhinorrhea and nasal itching in 3 to 5 minutes while INS can inhibit the underlying mucous allergic inflammation and is recommended as the first-line medication for moderate-to-severe AR INS combined AH1 have shown a synergic effect on control AR inflammation and provide rapid AR symptom relief Investigators hypothesis that the on-demand administration of INS combined AH1 can achieve similar AR control level with less dosing frequency as compared to the daily INS maintenance in controlled moderate-to-severe AR patients
Intranasal AH1 can relieve AR symptoms including sneezing rhinorrhea and nasal itching in 3 to 5 minutes while INS can inhibit the underlying mucous allergic inflammation and is recommended as the first-line medication for moderate-to-severe AR INS combined AH1 have shown a synergic effect on control AR inflammation and provide rapid AR symptom relief Investigators hypothesis that the on-demand administration of INS combined AH1 can achieve similar AR control level with less dosing frequency as compared to the daily INS maintenance in controlled moderate-to-severe AR patients
Detailed Description:
BackgroundSignificance The prevalence of AR is increasing worldwide A large number of studies have shown that AR has a significant adverse impact on the quality of life especially in the moderate-to-severe AR population However as AR is not a fatal disease only a small proportion of AR patients will go to hospital to seek professional medical advice They have a tendency to do so only when their AR-related symptoms become intolerable which led to a dramatic low level of AR control It is well known that uncontrolled AR has been identified as a high-risk factor of exacerbation of asthma and chronic rhinosinusitis In AR patients 40 will develop asthma and up to 30 will develop chronic sinusitis Adequate treatment of AR always help to improve patients quality of life and also reduce the risk of AR related complications
To achieve the goal of AR control long-term treatment is always needed AR is an IgE-mediated inflammatory disease induced by allergen exposure Our previous study had shown that more than 90 of AR patients in central China were induced by house dust mite HDM a perennial indoor allergen HDM exposure leads to persistent allergic inflammation in nasal mucous and causes periodic exacerbation of AR symptoms INS is currently the cornerstone medication to inhibit the allergic inflammation and is recommended as the first-line medication for moderate-to-severe AR However the anti-inflammation effect can only be achieved after administrate for several days to two weeks For this reason the ARIA guideline suggests to use INS regularly for 2-4 weeks then step down gradually In another side antihistamine belongs to symptom-relief medication which has been proven to act within 5min for nasal spray and 30min for oral route Antihistamine is also recommended as first-line medication for mild AR patients and combined with INS for moderate-to-severe AR patients Our previous studies had shown that if AR patients were treated according to the current guideline for 15 days only 723 of them were controlled However if the treatment extended to 60 days more than 95 would achieve AR controlled
Low adherence is always a considerable issue for long-term treatment In asthma patients more than 80 of patients taken β2 agonist as needed to relieve their symptom instead of daily using inhalant corticosteroids For AR the adherence to treatment recommendation was below 30 in the real world Most AR patients wouldnt take their medication continuously for 14 days as they usually suffered from several episodes of short-term AR symptoms They have a strong preference for a treatment which can provide both a rapid onset of action and clinically-relevant symptom relief
In this study investigators will compare the AR control level of on-demand treatment versus daily maintenance treatment in moderate-to-severe AR patients If the on-demand treatment can achieve similar or non-inferior AR control rate as daily maintenance treatment it will be very helpful to optimize current management of AR patients
Preliminary Data A recent study in 150 pollen-induced AR children found that the percentage of symptom-free-day was in favor of INS on-demand 30 compared with low dosage INS daily 22 although the statistical significance was not achieved It implied that on-demand fluticasone propionate treatment was at least as effective as a regular treatment at a lower dose The authors concluded that an on-demand INS strategy has the advantage of a lower overall corticosteroid exposure and less costs
Two large randomized controlled studies in mild asthma patients 4215 and 3849 patients were randomized respectively also shown that budesonide-formoterol used as needed was non-inferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment
Investigators have validated the Allergic Rhinitis Control Test ARCT questionnaire in 255 AR Chinese patients the ARCT score 20 was regard as controlled AR Investigators also validated ARCT questionnaire in guiding stepwise treatment in 510 AR patients Thus the ARCT questionnaire will be used to calculate the AR control level in our study In our randomized controlled trial 129 AR patients received INS without dosage adjustment for 60 days 858 were controlled AR ARCT score20 In a hospital based study investigators found that only 48 of the AR patients were controlled without taken medication or taken medication occasionally However the data could not reflect the real-life situation as usually only the intolerable symptoms would drive AR patients to the hospital There is still lack of data of AR control rate in on-demand treatment patients
Research Design and Methodology Study Design This is an open-labeled randomized controlled clinical study with HDM-related AR which will be conducted in four multicenter in Central China The symptom uncontrolled moderate-severe AR patient were enrolled with ARCT20 In the run-in period AR patients will be treated with INS plus AH1 twice daily for 2 weeks and assessed with ARCT questionnaire and Quality-of-Life Questionnaires If AR is controlled the patients will be randomized into on-demand INS combine intranasal AH1 group on-demand INS or daily INS maintenance group and treat for 4 weeks then the treatment will be stopped and the patients will be followed up for another 8 weeks During the study period the patients have to fill in the diary card every day to record TNSS and daily ARCT every day During the run-in period the treatment and follow-up period the patients were followed up every 4 weeks in the hospital to finish ARCT RQLQ and IPQ questionnaires to compare the AR control and recurrence time among the three groups
Study Population This is a multi-center study Patients with persistent moderate-to-severe AR will be enrolled after sign the informed and content form adolescents need guardian consent
Inclusion Criteria 1 18-65 years old2 AR patients according to ARIA guidelines3 Mono-sensitized to HDM and had AR symptoms after HDM exposure 4 had at least 2 nasal symptomssneezing runny nose itching nasal congestion in the screening period4 ARCT score 20 after 2-week INS combined with AH1 treatment at run-in period5 had adequent informed and given their consent to participate in the study
Exclusion Criteria
1 Pregnant or lactating women patients with malignant tumor patients with congenital or acquired immunodeficiency disease patients with mental illness2 Acute upper respiratory infection in the run-in period3 History of chronic sinusitis with nasal polyps4 Severe deviation of nasal septum5 received allergen immunotherapy in the past 5 years6 received biological therapy in the past 6 months 7Acute upper respiratory tract infection in run-in period8 Patients who failed to achieve AR control in the run-in period9 Patients who are participating in other clinical trials 10 patients who are not suitable for this clinical trial due to other reasons evaluated by investigators
Study protocol
1 Enroll HDM mono-sensitized AR patients
2 Diagnosis and differential diagnosis were made according to ARIA The other related diseases that may increase nasal symptoms were excluded according to ARIA
3 Evaluate ARCT score RQLQ and Brief IPQ questionnaire in the baseline Treat with intranasal Azelastine and Fluticasone Propionate and re-evaluate ARCT score to assure ARCT20 after 2 weeks before randomization During the run-in period the patients need to complete the daily TNSS and the daily ARCT on-line
4 Randomize into On-demand intranasal Azelastine and Fluticasone Propionate group on-demand Fluticasone Propionate group or daily intranasal Fluticasone maintenance group The patients have to complete the dairy online to record the TNSS and ARCT
5 The pharmacotherapy will be stopped after 4 weeks and the patients will be followed up for another 8 weeks During the follow-up period the patients filled the diary card every day to recorded TNSS and ARCT During the treatment and follow-up period the patients have to revisit every 4 weeks in the hospital ARCT RQLQ and IPQ questionnaires were filled in to compare the AR control and recurrence time among the three groups
Statistical Approach and sample size calculation Referring to the relevant literature investigators assume the AR control rate of continuous NCS treatment group will be 85 and the AR control rates of on-demand NCS group and on-demand NCS AH1 group both will be 75 investigators also set the non-inferiority margin value as 10 and the enrollment ratio as 111 The sample size of each group is 49 plus 20 drop-out rate a total of 180 cases are required in this trial
Possible risks and preventive measures Fluticasone propionate nasal spray and azelastine hydrochloride nasal spray used in this study have been approved and widely used in AR patients for many years in China The common local adverse reactions include epistaxis nasal cavity and throat dryness local nasal pain and irritation bitter taste or nausea etc Systemic adverse reactions are rare Any adverse events will be recorded and managed by the investigators according to Good Clinical Practice guidelines
Data collection and statistical analysis Data collection the patients filled in the diary on-line every day to record the nasal symptom TNSS score and ARCT The symptoms included nasal itching sneezing runny nose and nasal congestion The scoring criteria were 0 asymptomatic 1 mild 2 moderate and 3 severe The ARCT score was used to assess the control of AR symptoms During the treatment and follow-up period the patients were followed up every 4 weeks on-site ARCT RQLQ and IPQ questionnaires were filled in to compare the AR control and recurrence among the three groups
Statistical analysis the primary endpoint was AR control level at 4-week among the treatment groups The secondary endpoint included TNSS scores of different treatment groups AR recurrence time after treatment RQLQ and IPQ questionnaire score comparison and adverse events among different treatment groups The data of continuous variables were tested for normality and the variables in accordance with normal distribution were expressed by mean standard deviation T test was used to compare the differences between groups The variables of non-normal distribution were expressed by median quartile interval Mann Whitney U test was used to compare the differences between groups For binary variables Chi square test was used to determine the difference between groups Kaplan Meier survival curve was used to analyze the recurrence time of AR in different treatment groups A p value less than 005 was considered statistically significant
To achieve the goal of AR control long-term treatment is always needed AR is an IgE-mediated inflammatory disease induced by allergen exposure Our previous study had shown that more than 90 of AR patients in central China were induced by house dust mite HDM a perennial indoor allergen HDM exposure leads to persistent allergic inflammation in nasal mucous and causes periodic exacerbation of AR symptoms INS is currently the cornerstone medication to inhibit the allergic inflammation and is recommended as the first-line medication for moderate-to-severe AR However the anti-inflammation effect can only be achieved after administrate for several days to two weeks For this reason the ARIA guideline suggests to use INS regularly for 2-4 weeks then step down gradually In another side antihistamine belongs to symptom-relief medication which has been proven to act within 5min for nasal spray and 30min for oral route Antihistamine is also recommended as first-line medication for mild AR patients and combined with INS for moderate-to-severe AR patients Our previous studies had shown that if AR patients were treated according to the current guideline for 15 days only 723 of them were controlled However if the treatment extended to 60 days more than 95 would achieve AR controlled
Low adherence is always a considerable issue for long-term treatment In asthma patients more than 80 of patients taken β2 agonist as needed to relieve their symptom instead of daily using inhalant corticosteroids For AR the adherence to treatment recommendation was below 30 in the real world Most AR patients wouldnt take their medication continuously for 14 days as they usually suffered from several episodes of short-term AR symptoms They have a strong preference for a treatment which can provide both a rapid onset of action and clinically-relevant symptom relief
In this study investigators will compare the AR control level of on-demand treatment versus daily maintenance treatment in moderate-to-severe AR patients If the on-demand treatment can achieve similar or non-inferior AR control rate as daily maintenance treatment it will be very helpful to optimize current management of AR patients
Preliminary Data A recent study in 150 pollen-induced AR children found that the percentage of symptom-free-day was in favor of INS on-demand 30 compared with low dosage INS daily 22 although the statistical significance was not achieved It implied that on-demand fluticasone propionate treatment was at least as effective as a regular treatment at a lower dose The authors concluded that an on-demand INS strategy has the advantage of a lower overall corticosteroid exposure and less costs
Two large randomized controlled studies in mild asthma patients 4215 and 3849 patients were randomized respectively also shown that budesonide-formoterol used as needed was non-inferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment
Investigators have validated the Allergic Rhinitis Control Test ARCT questionnaire in 255 AR Chinese patients the ARCT score 20 was regard as controlled AR Investigators also validated ARCT questionnaire in guiding stepwise treatment in 510 AR patients Thus the ARCT questionnaire will be used to calculate the AR control level in our study In our randomized controlled trial 129 AR patients received INS without dosage adjustment for 60 days 858 were controlled AR ARCT score20 In a hospital based study investigators found that only 48 of the AR patients were controlled without taken medication or taken medication occasionally However the data could not reflect the real-life situation as usually only the intolerable symptoms would drive AR patients to the hospital There is still lack of data of AR control rate in on-demand treatment patients
Research Design and Methodology Study Design This is an open-labeled randomized controlled clinical study with HDM-related AR which will be conducted in four multicenter in Central China The symptom uncontrolled moderate-severe AR patient were enrolled with ARCT20 In the run-in period AR patients will be treated with INS plus AH1 twice daily for 2 weeks and assessed with ARCT questionnaire and Quality-of-Life Questionnaires If AR is controlled the patients will be randomized into on-demand INS combine intranasal AH1 group on-demand INS or daily INS maintenance group and treat for 4 weeks then the treatment will be stopped and the patients will be followed up for another 8 weeks During the study period the patients have to fill in the diary card every day to record TNSS and daily ARCT every day During the run-in period the treatment and follow-up period the patients were followed up every 4 weeks in the hospital to finish ARCT RQLQ and IPQ questionnaires to compare the AR control and recurrence time among the three groups
Study Population This is a multi-center study Patients with persistent moderate-to-severe AR will be enrolled after sign the informed and content form adolescents need guardian consent
Inclusion Criteria 1 18-65 years old2 AR patients according to ARIA guidelines3 Mono-sensitized to HDM and had AR symptoms after HDM exposure 4 had at least 2 nasal symptomssneezing runny nose itching nasal congestion in the screening period4 ARCT score 20 after 2-week INS combined with AH1 treatment at run-in period5 had adequent informed and given their consent to participate in the study
Exclusion Criteria
1 Pregnant or lactating women patients with malignant tumor patients with congenital or acquired immunodeficiency disease patients with mental illness2 Acute upper respiratory infection in the run-in period3 History of chronic sinusitis with nasal polyps4 Severe deviation of nasal septum5 received allergen immunotherapy in the past 5 years6 received biological therapy in the past 6 months 7Acute upper respiratory tract infection in run-in period8 Patients who failed to achieve AR control in the run-in period9 Patients who are participating in other clinical trials 10 patients who are not suitable for this clinical trial due to other reasons evaluated by investigators
Study protocol
1 Enroll HDM mono-sensitized AR patients
2 Diagnosis and differential diagnosis were made according to ARIA The other related diseases that may increase nasal symptoms were excluded according to ARIA
3 Evaluate ARCT score RQLQ and Brief IPQ questionnaire in the baseline Treat with intranasal Azelastine and Fluticasone Propionate and re-evaluate ARCT score to assure ARCT20 after 2 weeks before randomization During the run-in period the patients need to complete the daily TNSS and the daily ARCT on-line
4 Randomize into On-demand intranasal Azelastine and Fluticasone Propionate group on-demand Fluticasone Propionate group or daily intranasal Fluticasone maintenance group The patients have to complete the dairy online to record the TNSS and ARCT
5 The pharmacotherapy will be stopped after 4 weeks and the patients will be followed up for another 8 weeks During the follow-up period the patients filled the diary card every day to recorded TNSS and ARCT During the treatment and follow-up period the patients have to revisit every 4 weeks in the hospital ARCT RQLQ and IPQ questionnaires were filled in to compare the AR control and recurrence time among the three groups
Statistical Approach and sample size calculation Referring to the relevant literature investigators assume the AR control rate of continuous NCS treatment group will be 85 and the AR control rates of on-demand NCS group and on-demand NCS AH1 group both will be 75 investigators also set the non-inferiority margin value as 10 and the enrollment ratio as 111 The sample size of each group is 49 plus 20 drop-out rate a total of 180 cases are required in this trial
Possible risks and preventive measures Fluticasone propionate nasal spray and azelastine hydrochloride nasal spray used in this study have been approved and widely used in AR patients for many years in China The common local adverse reactions include epistaxis nasal cavity and throat dryness local nasal pain and irritation bitter taste or nausea etc Systemic adverse reactions are rare Any adverse events will be recorded and managed by the investigators according to Good Clinical Practice guidelines
Data collection and statistical analysis Data collection the patients filled in the diary on-line every day to record the nasal symptom TNSS score and ARCT The symptoms included nasal itching sneezing runny nose and nasal congestion The scoring criteria were 0 asymptomatic 1 mild 2 moderate and 3 severe The ARCT score was used to assess the control of AR symptoms During the treatment and follow-up period the patients were followed up every 4 weeks on-site ARCT RQLQ and IPQ questionnaires were filled in to compare the AR control and recurrence among the three groups
Statistical analysis the primary endpoint was AR control level at 4-week among the treatment groups The secondary endpoint included TNSS scores of different treatment groups AR recurrence time after treatment RQLQ and IPQ questionnaire score comparison and adverse events among different treatment groups The data of continuous variables were tested for normality and the variables in accordance with normal distribution were expressed by mean standard deviation T test was used to compare the differences between groups The variables of non-normal distribution were expressed by median quartile interval Mann Whitney U test was used to compare the differences between groups For binary variables Chi square test was used to determine the difference between groups Kaplan Meier survival curve was used to analyze the recurrence time of AR in different treatment groups A p value less than 005 was considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None