Grass Pollen Subcutaneous Immunotherapy in Elderly Patients (SCITelderly)
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|ClinicalTrials.gov Identifier: NCT02440243|
Recruitment Status : Completed
First Posted : May 12, 2015
Last Update Posted : May 12, 2015
|First Submitted Date ICMJE||April 22, 2015|
|First Posted Date ICMJE||May 12, 2015|
|Last Update Posted Date||May 12, 2015|
|Study Start Date ICMJE||January 2011|
|Actual Primary Completion Date||September 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Grass Pollen Subcutaneous Immunotherapy in Elderly Patients|
|Official Title ICMJE||Grass Pollen Subcutaneous Immunotherapy: a Double-blind, Placebo-controlled Study in Elderly Patients With an Allergy to Grass Pollen|
Background There is limited evidence indicating that specific immunotherapy in elderly patients is safe and effective. This study was performed to evaluate the safety and efficacy of specific subcutaneous immunotherapy (SCIT) against grass pollen allergens in patients over 60 years of age with seasonal allergic rhinitis (SAR) and a confirmed allergy to grass pollen.
Objective This study assessed the safety and efficacy of SCIT for grass pollen allergens in elderly patients with SAR.
Methods This study included 62 60- to 75-year-old patients with SAR and grass pollen allergy confirmed using a skin prick test, nasal provocation, and serum IgE measurement. The patients were individually randomized to the active or placebo groups using a double-blinded method. There were 33 subjects in the SCIT group (Purethal, Grass pollen, HAL Allergy B.V, Leiden, Netherlands) and 29 subjects in the placebo group monitored for three years. The patients were required to record each use of anti-allergy medication in a diary and use a visual graphic scale. The main outcome measure was the area under the curve (AUC) for the combined symptom and medication score (SMS).
Methods Patients A total of 109 patients ranging from 60 to 70 years of age were recruited from the outpatient allergy clinic to assess their eligibility for inclusion in the study. The subjects had moderate or severe intermittent allergic rhinitis and fulfilled the ARIA criterion. Additionally, the patients included in the study all had a positive skin prick test (SPT), were positive for specific immunoglobulin E (sIgE), and had positive nasal provocation tests (NPTs) with grass pollen mixture allergens. Patients with any of the following characteristics were excluded from the study: hypersensitivity to other allergens, bronchial asthma, non-allergic rhinitis (especially senile or vasomotor rhinitis) and severe non-stable diseases. However, patients with stable coronary disease, diabetes, and arterial hypertension were permitted in the study. All subjects were required to abstain from anti-allergy drugs and glucocorticoid nasal drops for at least 6 weeks prior to the start of the study.
There were 62 patients individually randomized in comparable numbers to one of two "parallel" groups using a double-blind method. The groups were the active (n=33) treatment group and the placebo (n=29) group. There were 31 subjects in the SCIT group and 25 subjects in the placebo group that completed the three-year observation period. The groups were comparable at baseline.
Diagnostic procedures A careful examination of the eyes, ears, nose, and throat was performed on all patients. The severity of seasonal allergic rhinitis (SAR) was assessed using the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The patients with other nasal problems such as chronic nasal obstruction, reduced olfaction, bacterial colonization, and chronic sinusitis were diagnosed based on a CT scan and nasal endoscopy. Several patients were excluded from further observation as a result of these problems. The subjects with other chronic or acute clinical disorders or with a history of respiratory tract infections within four weeks of the study initiation were also excluded. The SPT was performed using inhalant allergens (HAL Allergy B.V, Leiden, Netherlands) from the following panel: D. pteronyssinus, D. farinae, mixed 5 grasses (Phleum pratense, Dactylis glomerata, Anthoxanthum odoratum, Lolium perenne, and Poa pratensis), mixed tree, mugwort, Alternaria, Cladosporium, dog and cat allergens. There were also positive (10 mg/ml of histamine) and negative (saline) controls included. A grass pollen allergy was defined as having positive skin tests for 5 grass pollen allergens with a minimum wheal diameter of at least 3 mm greater than the negative control. The patients with negative tests for histamine sensitivity were excluded from further analyses. The sIgE reactivity to the single grass pollen allergen components (Phl p1, Phl p2, Phl p5, Phl p6, Phl p7 and Phl p12) was determined using ImmunoCAP (Phadia AB, Uppsala, Sweden) tests. The results were considered positive when the sIgE concentration was greater than 0.35 IU/ml (according to the manufacturer's instructions). NPTs were conducted using active anterior rhinomanometry with commercial grass pollen mixture allergens. The concentration was 10,000 AU/ml and the mixture was delivered as 1 puff per nostril (HAL Allergy B.V, Leiden, Netherlands) using the methods described by Bachert et al. and Dordal et al. A reduction in the peak nasal inspiratory flow greater than or equal to 40% and an increase in symptoms greater than or equal to 5 points were considered to be positive NPT criteria by Bachert et al. and Dordal et al. The NPTs were also repeated after three years of treatment. The patients monosensitized to grass pollen were included in this study.
Treatments The patients were randomly selected to receive Purethal Grasses 20,000 AUM/ml (pollen mixture extract solution of Agrostis stolonifera, Anthoxanthum odoratum, Arrhenatherum elatius, Dactylis glomerata, Festuca rubra, Holcus lanatus, Lolium perenne, Phleum pratense, Poa pratensis, Secale cereal, Loe edasi HAL Allergy B.V, Leiden, Netherlands) or placebo. The recruitment period was limited to three months (October-December). Purethal grasses (January-April) were administered as pre-seasonal therapy using the following regimen: 1 dose- 0.1 ml, 2 dose - 0.2 ml, 3 dose - 0.4 ml every week, and doses 4- 7 consisted of 0.5 ml every two weeks.
Using this schedule the average cumulative dose was 460,500 BAU (Bioequivalent Allergy Unit), which contains approximately 690 μg of Phl p5 administered to each patient undergoing active treatment for all three years of the study. The study consisted of two phases. The first phase was the baseline one season of follow-up visits without treatment and the second phase was three years of SCIT or placebo.
Assessment of efficacy The prime outcome measure was the area under the curve (AUC) for combined symptom and medication score (SMS) over the grass pollen season for baseline 2010 (before treatment) and in 2011, 2012 and finally in 2013 after three years of SCIT. The patients recorded symptom severity in a daily diary during the pollen season (May-August) by scoring the following areas: nasal itching, sneezing, running, blockage, and ocular itch on a separate Visual Analog Scale (VAS) with a continuous scale from 0 cm (no symptoms) to 10 cm (very severe symptoms). The rescue medication provided and scoring was a one point per spray for Azelastine nasal spray or eye drops (Levocabastine), or per 5 mg levocetirizine tablet. The score was two points per puff for mometasone fuorate nasal spray and three points per prednisolone 10 mg tablet. This combined symptom-medication score was calculated as a sum of the symptom score and medication score monitored daily with the use a diary as described. The SMS was derived by adding the VAS for each of these five symptoms.
The secondary outcome measures included quality of life, reduction of symptoms score, safety assessment and monitoring of IgG4. The local reactions were assessed at 30 min after injection and measured in cm. The systemic reactions were graded according to EAACI criteria.
Serum IgG4 measurements The serum concentration of IgG4 against birch alder and hazel pollens were determined in blood serum by ELISA tests according Lai et al. before and after the three-year SIT.
Quality of life Patient quality of life was evaluated with the RQLQ score for adults using questionnaires every grass pollen season during the study.
Pollen counts The local grass pollen counts were determined by volumetric pollen trap (Burkard, Scientific Ltd, Uxbridge, UK). The peak pollen count was defined as the day with highest grass pollen count for each season 3 weeks before and 3 weeks after the peak grass pollen count.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Study Arms ICMJE||
|Publications *||Bozek A, Kolodziejczyk K, Krajewska-Wojtys A, Jarzab J. Pre-seasonal, subcutaneous immunotherapy: a double-blinded, placebo-controlled study in elderly patients with an allergy to grass. Ann Allergy Asthma Immunol. 2016 Feb;116(2):156-61. doi: 10.1016/j.anai.2015.12.013.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Actual Enrollment ICMJE||Same as current|
|Actual Study Completion Date ICMJE||December 2014|
|Actual Primary Completion Date||September 2014 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||60 Years to 75 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Not Provided|
|Removed Location Countries|
|NCT Number ICMJE||NCT02440243|
|Other Study ID Numbers ICMJE||MC56871/12|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Andrzej Bozek, Medical University of Silesia|
|Study Sponsor ICMJE||Medical University of Silesia|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||Medical University of Silesia|
|Verification Date||May 2015|
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