[Summary text]
Skal nasasteriod bruges frem for perorale antihistaminer til behandling af persisterende allergisk rhinitis?
Tilstoppet næse (kritisk)
Næseflod, kløe og/eller nysen (kritisk)
Livskvalitet (vigtig)
Fraværsdage fra arbejde/skole (vigtig)
Øjensymptomer (vigtig)
Døsighed (vigtig)
Næseblødning (vigtig)
Knoglebrud (vigtig)
Diabetes (vigtig)
Væksthæmning (vigtig)
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: The study patients were 8- to 17-year-old children with adocumented history of SAR, positive response to a skin pricktest (wheal 3-mm greater than negative control or equal to thepositive control) for seasonal aeroallergens, and clinicallyidentifiable symptoms at the time of randomization.
Excluded criteria: The study patients were 8- to 17-year-old children with adocumented history of SAR, positive response to a skin pricktest (wheal 3-mm greater than negative control or equal to thepositive control) for seasonal aeroallergens, and clinicallyidentifiable symptoms at the time of randomization.
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Dichotomous:
Sponsorship source: This research was supported by a grant from GlaxoSmithKiine.
Country: US
Setting:
Comments:
Authors name: Bender
Institution: Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado
Email: benderb@njc.org
Address: 1400 Jackson stDenver, CO 802006
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Elisabeth Ginnerup-Nielsen
Continuous outcomes:
Elisabeth Ginnerup-Nielsen Quality of Life Questionnaire, meassured with adolescent rhinoconjunctivitis Quality of Life Questionnaire25 items self reported quality-of-life measure designed specifical)y for patients aged 12 to 17 years with allergic rhinoconjunctivitis. The rating for those domains is on a 7-point scale from "not troubled" to "extremely troubled" (activity, nasal, nose/eye, eye, and emotions)Desuden bruges Treatment Outcome Question Scores· til rhinorrhea/itching/sneasing med spørgsmålet:"How do you feel that the study drug has controlled yourchild's allergic rhinitis symptoms in the last week?"
Dichotomous outcomes:
Adverse outcomes:
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: rhinitis symptom score of 24 points or greater on 4 of the 5 baseline days according to a 4-point scale for the five symptoms evaluated (nasal congestion, rhinorrhea, nasal itch, sneezing, andocular symptoms): 0 = none; symp toms absent; 1 = mild; symptoms present but not annoying; 2 = moderate; symptoms present and annoying; and 3 = severe; symptoms interfere with daily activities or sleep. Tue max imum symptom score any patient could record in four days was 60.
Excluded criteria: Patients were excluded from the study if they had clinically significant abnormalities on physical examination or in urinalysis, hematology, or serum chemistry test results; nasal candidiasis, acute or chronic sinusitis, significant na sal polyposis or septum deviation; or rhi nitis medicamentosa. Women who were pregnant, lactating, or of childbearing potential and not practicing an approved method of contraception were excluded from the study. Recent or regular use of any of the foliowing medications was an exclusion criterion: topical corticosteroids, intranasal cromolyn, topical decongestants, systemic steroids, long-acting antihista mines, or investigational drugs.Patients were also excluded if they had a history of habitual abuse of nasal decongestants; used medication for an other indication that might cause, sup press, or exacerbate the symptoms of seasonal allergic rhinitis; or had a his tory of hypersensitivity or nonresponse to topical steroids or antihistamines
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Dichotomous:
Sponsorship source: Rhone-Poulenc Rorer Pharmaceuticals Inc.Collegeville.Pensylvania
Country: US
Setting:
Comments:
Authors name: John Condemi
Institution: Private practice, Rochester, New York
Email:
Address: Astma and Allergy919 Westfall rd Bldg BRochester NY 14618
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Elisabeth Ginnerup-Nielsen Rhinocon junctivitis Quality of Life Question naire (RQLQ) at visits 2, 3, and 4. The questionnaire had seven dimensions:(1) activities, (2) emotions, (3) eye symptoms, (4) nasal symptoms, (5) non-hay fever problems, (6) practical problems, and (7) sleep. Subjects' quality of life in each dimension was assessed. Response options for each question were on a 0 to 6 scale. The mean dimension scores had a range from 0 to 6. Overall quality of life was the mean for all questions and also had a range from 0 to 6.Emotions er valgt ud i samråd med Morten
Dichotomous outcomes:
Adverse outcomes:
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: > 12 years, history of SAR, Positive prick test to seasonal allergens.
Excluded criteria: Childbearing potential. inhalation medicin, corticosteroids, Nasal abnormalities.
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Sponsorship source: Glaxo laboratories
Country: France
Setting:
Comments:
Authors name: P. Gehanno
Institution: Oto.Rhino-Laryngologie Hospital Claude Bernard Paris
Email:
Address: Unite Respiratoire43 Rue Vineuse75116 ParisFrance
Identification:
Participants:
Study design:
Baseline characteristics:
Elisabeth Ginnerup-Nielsen duration of rhinitis opgivet i %
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Elisabeth Ginnerup-Nielsen symptomer opgjort uden sd CI eller lignende. Forfatter er kontaktet i uge 3 2015 for oplysninger om dettePÅ en overall 0-3 symptom scale (3 = worse) af (obstruction, rhinorhhea, sneezing, itching) scores.2.5 intervention (N= 57)4 control gruppe (N= 57)
Dichotomous outcomes:
Adverse outcomes:
From updating search
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: 12-17 years of age. Pos prick-test to ragweed extract. Moderate to severe SAR.
Excluded criteria: Perennial rhinitis. medicin affecting rhinitis. Corticosteroids.structural nasal abnormalities or concurrent disease interfering study results.
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Sponsorship source: Supported by Glaxo Canada, Inc
Country: Canada
Setting:
Comments:
Authors name: Gloria Jordana,
Institution: Department of Pediatrics, McMaster University, Hamilton; bDepartment of Medicine, Queens University, Kingston
Email:
Address: Jerry Dolovich, MD, McMaster University Medical Centre, 1200 Main St. West, Room 3V41 Hamilton, Ontario L8N 3Z5, Canad
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Elisabeth Ginnerup-Nielsen Der er opgivet symtomer uden sd eller lignende usikkerhed. Forfatterne er kontaktet i uge 3 om disse værdier.assessment at 28 days
Dichotomous outcomes:
Adverse outcomes:
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label: YES
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: > 18 years of age. history of SAR during last 2 seasons.Pos ragweed skin prick test.
Excluded criteria: Renal,hepatic or cardiovascular disease.nasal abnormalities. perennial rhinitis. corticosteroids. nasal medicin. pregnant or lactating. immunotherapy.
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Sponsorship source: Glaxo-wellcome
Country: US
Setting:
Comments:
Authors name: Scott M Kaszuba
Institution: Otolaryngology-head and neck, department of surgery, the Pritzker school of medicine
Email: rnacleri@surgery.bsd.uchicago.edu
Address: university of Chicago, 5841 S Maryland Ave, mail code 1035,Chicago, IL 60637
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Elisabeth Ginnerup-Nielsen outcome described without sd. Quality of life was assessed with the self-administered RQLQas described and validated by Juniper and Guyatt.10In brief,the RQLQ has 7 domains: sleep, non–nasal/eye, practical,nasal, eye, emotional, and activity. The average score foreach domain was computed and used for data analysis. higher=worse
Dichotomous outcomes:
Adverse outcomes:
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: Male and nonpregnant female outpatients, aged 12 years or older, were eligible for the study if they had moderate to severe seasonal allergic rhinitis diagnosed according to four criteria: (1) positive (a 2+ reaction, scored on a scale of 0 to 4, defined as a wheal diame ter at least 3 mm greater than diluent control) skin test reaction to mountain cedar (Junipenis ashei) allergen within 12 months; (2) appearance of the nasal mucosa consistent with a diagnosis of seasonal allergic rhini tis; (3) a history of seasonal onset and offset of symp toms for at least two previous mountain cedar pollen seasons; and (4) moderate to severe symptoms of rhinitis evidenced by patient diary card ratings during a run-in.
Excluded criteria: Patients were ineligible for the study if they had received, before the screening visit, treatment with loratadine within 1 week, astemizole within 6 weeks, cromolyn sodium within 2 weeks, over-the counter or prescrtption medications that could affect rhinitis symptomatology (eg, nasal decongestants) within 72 hours, or inhaled, intranasal, or systemic cor ticosteroids within 1 month. Patients could not have either a septal deviation (>50% blockage) or a nasal polyp that could obstruct penetration of an intranasal spray. Patients were not included if they had a history of nasal septal surgery or nasal septal perforation. Patients were excluded if they had clinically signifi cant physical examination tindings at screening, had evidence of candidal infection, or were pregnant or lactating. Patients were also excluded if they had any condition or impairment that might affect their ability to complete the study or provide informed consent.
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Adverse Events:
Sponsorship source: This study was supporte<l by a granl from Glaxo Welkome Ine.
Country: US
Setting:
Comments:
Authors name: Paul H Ratner
Institution: San Antonio, Austin, and New Braunfels, Te:i:as;
Email:
Address: Paul H.Ratner; MD, Sylvana Research., 7711 Louis Pasteur Drive, Suit.e 406, San Antonio, TX 78229.
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Elisabeth Ginnerup-Nielsen withdrawals due to adverse events: 3 in intervention group and 2 in control - not further described.
Dichotomous outcomes:
Adverse outcomes:
Elisabeth Ginnerup-Nielsen . The most frequently reported drug-related adverse events were blood in the nasal mucus (1% to 2% in active treatment groups and 3% in the placebo group), ep s taxis (l% for all treatments), and xerostomia (2% for all treatments).
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intranasal fluticasone propionate
Ketotifen
Included criteria: 2 consecutive seasons of SAR. Positive skin test to ragweed.
Excluded criteria: pregnant and lactating women. signs of sinusitis, nasal pathology, drugs that might interfere vith rhinitis symtoms. Infections in the nose.
Intervention Characteristics
Intranasal fluticasone propionate
Ketotifen
Continuous:
Dichotomous:
Sponsorship source: Rhone-poulenc Rorer Pharma. Inc.
Country: US
Setting:
Comments:
Authors name: William Schoenwetter
Institution: Park Nicolet Medical center
Email:
Address: 3800 Park Nicollet Blvd. Minneapolis MN 55416
Identification:
Participants:
Study design:
Baseline characteristics:
Intervention characteristics:
Pretreatment:
Continuous outcomes:
Elisabeth Ginnerup-Nielsen Nasalstuffiness,rhinor-rhea,postnasaldrip,ocularsymptoms,sneezing,andnasalitchwereevaluated on 4 point scale
Dichotomous outcomes:
Adverse outcomes:
From updating search
Wrong study design
Wrong patient population
Wrong comparator
Wrong patient population
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
unclear
Comment: No information given on how the randomization was conducted.
Comment: unclear how
Quote from text:
a 1:1 ratio by a computer-generated randomization Comment: Computer generated sequence
Quote: "randomized, double-blind, parallel- group study"
Comment: unclear how sequence generation as done
Comment: Not described
Not described
Unclear
Quote: "were ran- domized in a 1: 1 ratio to 28"
Comment: Not described properly
The physician contacted the data-collecting center after evaluating the eligibility criteria of the patient. Patients who matched the eligibility criteria were registered in the study and assigned in accordance with the computer-generated random allocation table with a block size of 4 and 6.
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
unclear
Comment: Not described
Comment: Not described
It is not described how the allocation sequence was concealed.
Comment: Not described
Comment: not described
Not described
Comment: Not described
Comment: Not descrribed
To conceal the assignment sequence, central randomization was used, and the block size was not released.
Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Comment: . A double-dummy design was used: pa tients treated with TAA aqueous nasal spray received a placebo oral medica tion and patients treated with lorata dine received a placebo nasal spray. Each loratadine tablet was placed in side a capsule for blinding purposes
Quote: "Qualifying patients were randomly assigned to receive fluticasone propionate aqueous nasal spray 200 |ig (two 50-|ig sprays in each nostril) and placebo tablet, or loratadine (one 10-mg tablet) and placebo nasal spray (two sprays in each nos-"
The participants received identical nasal sprays, and we only use data from this study until the washout period - not the cross over period. In this way the personnel is blinded to who is getting better after the cross over.
Quote: "Subjects were randomly assigned to receive either FP aqueous nasal spray, 200 ~g plus placebo oral tablet, once daily each morning or placebo aqueous nasal spray and loratadine oral tablet, 10 mg, once daily each morning for the duration of the treatment period."
Comment: Double-blind double-dummy study - seems blinded
Comment: open label
Not described
Comment: Quite a lot described about dummies and placebo tabletsdouble-blind double-dummy study
Quote: "and 1 placebo cap- sule or placebo nasal spray (2 sprays per nostril) and 1 loratadine lo-mg capsule (loratadine tablet placed within a capsule)."
Comment: Double-blind double-dummy study
Additionally, our study did not involve
any blinding processes, which may have led to a po-
tential bias in the results.
Detection bias due to knowledge of the allocated interventions by outcome assessors
Comment: Not described but outcome self reported
Comment: "double blind" but unclear if this concerns assessors. But outcome selfreported
Comment: Double-blind double dummu study. and selfreported outcome
The potential for observer bias was avoided by the double-blind study design
Quote: "The primary efficacy assessment was the percentage of symptom-free days (score of 0) for nasal blockage during the day. Throughout the trial period, the subjects were also asked to keep a daily record of all medications taken and any side effects or problems they experienced."
Comment: Not relevant when outcome is patient reported
Quote: "Also, the use of blindly assessed objective measures reinforces our findings."
Not described
Comment: Selfreported outcome
Comment: Subjective selfreported outcomes
Additionally, our study did not involve
any blinding processes, which may have led to a po-
tential bias in the results.
Attrition bias due to amount, nature or handling of incomplete outcome data
Comment: No ITT analysis amount of pt's in each group and dropout unclear
Comment: Of the 176 patients in the loratadine group, 157 (89%) com pleted the study.. A total of 348 patients had both a baseline and post baseline effic;acy assessment and were included in the intent-to-treat analysis (174 TAA aqueous and 174 loratadine). Relatively small dropout and ITT91% and 89% respectively completed the study. The dropout groups are described an comparable.
Quote: "Eleven patients withdrew from the study. Two patients discontinued fluticasone propionate be- cause of lack of efficacy. Nine patients discontinued loratadine for the following reasons: lack of effi- cacy (n=4), adverse events («=2), failure to return {n=2), or noncompliance {n = l)."
Comment: Relatively small dropout
Supportive analyses were car- ried out on the intent-to-treat (ITT) population, which was defined as all patients who were randomized and received at least 1 dose of study medication. ITT analyses were propertly made.
Comment: dropout 30/240 - relatively small dropout and ITT analysis done.
Quote: "Eighty-eight subjects were enrolled into the study. There were 44 subjects randomized to each arm of the"
Quote: "There was a low dropout rate in both groups and no difference between"
It is unclear whether there is drop out, and if a proper imputation methods is used.
Comment: 95 % completion rate
Comment: low dropout
These analyses were
based on intent-to-treat.
Reporting bias due to selective outcome reporting
Comment: No trial protocol. Strange that there is no symptom score?
Comment: No trial protocol but relevant outcome seems assessed
Comment: outcome unclearly reported
This study only presents data on 'Growth' which the study title tells us it will. No protocol located.
Comment: unclearly reported outcomes
They describe an approved protocol, but it has not been possible to find
Comment: No trial protocol but outcome assessed
Comment: No trial protocol but relevant outcomes seem reported
Relevant outcomes presented and trials was registered before taking place:
The clinical
trial registration number is UMIN000000575 (www.
umin.ac.jpctrindexhtm)Protocol?
Bias due to problems not covered elsewhere in the table
unclear
Varying results when you look at each patient. Some have a larger growth when treated with intervention and others have a larger growth when treated with placebo.
Comment: unclear how medication was used
This study is lacking of information; it is not to tell whether they are not following prescribed protocol or if they write in another form than standard studies are written from.
This study was performed as an open label study. It is unknown if other bias, than those already assess, could have influenced on the results.