Table 1 Characteristics of RCTs included in the analysis

Aubier, 2001¹¹

Open-label, parallel-group 8 weeks

Adults (18–75 years) with ≥4-week clinical history of moderate to severe asthma from 31 medical centers

BDP 800 μg/day via HFA-pMDI

(n = 101 ITT)

High dose

FP 1000 μg via HFA-pMDI

(n = 97 ITT)

High dose

AM PEF (L/min), PM PEF (L/min), FEV₁ (L), patients free from daily asthma symptoms (%), patients using SABA rescue medication (%)

Equivalence demonstrated for AM PEF: CI within ±25 L/min

Currie, 2002¹²

Single-blind, crossover 3 weeks per Tx period

Patients (mean [SE] age = 38 [4] years) with mild to moderate asthma

FP 500 μg/d via HFA-pMDI

(n = 20 ITT)

Medium dose

BDP 500 μg/d via HFA-pMDI

(n = 20 ITT)

Medium dose

Methacholine PD_20, (μg), exhaled tidal NO (ppb), FEV₁ (% predicted), AM PEF (L/min)

None

FP 1000 μg/d via HFA-pMDI

(n = 20 ITT)

High dose

BDP 1000 μg/d via HFA-pMDI

(n = 20 ITT)

High dose

Methacholine PD_20, (μg), exhaled tidal NO (ppb), FEV₁ (% predicted), AM PEF (L/min)

None

Fairfax, 2001¹³

Double-blind, double-dummy, parallel-group 6 weeks

Patients 18–65 years with at least a 4-week past history of clinically diagnosed asthma from 30 general practice sites

BDP 400 μg/d via HFA-pMDI

(n = 88 ITT)

Medium dose

FP 400 μg/d via CFC-pMDI

(84 ITT)

Medium dose

PEFR (L/min), FEV₁ (L)

Equivalence demonstrated for AM PEFR: CI within ±25 L/min

Ohbayashi, 2008¹⁴

Double-crossover (results presented from parallel-group analysis of first stage of study)

3 months per Tx

Patients (FP group mean age (years): 61.0 ± 17.4; BDP group mean age: 67.9 ± 13.1) with mild to moderate persistent asthma controlled with FP Diskus for ≤6 months

FP dose dependent on patient, via Diskus

(n = 25)

BDP Same dose as FP, via HFA-pMDI

(n = 24)

VC, FVC, FEV₁, MEFR, PEF (all % predicted),

FEF_50% (L/s), FEF_75% (L/s)

None

Robroeks, 2008¹⁵

Crossover

3 months per Tx

Children (6–12 years) with moderate persistent asthma from outpatient clinic

BDP 200 μg/d via HFA-pMDI

(n = 30)

Low dose

FP 200 μg/d via DPI

(n = 30)

Low dose

Absolute measures at end of treatment:

FEV₁, FVC, MEF₅₀ (all % predicted), FEV₁/VC (%)

None

Thongngarm, 2005¹⁶

Open-label

3 months

Patients (≥18 years) with 6-month history of asthma

BDP 320 μg/d via HFA-pMDI

(n = 20 ITT)

Medium dose

FP 330 μg/d via CFC-pMDI

(n = 10 ITT)

Medium dose

FEV₁, FVC, FEF_25–75% (all % predicted), CV (L), CV-VC, post-bronchodilator TLC, TGV, RV, FEV₁, FVC, FEF_25–75% (all % predicted), AM PEF, night-time awakening, shortness of breath, chest tightness, wheezing, cough, phlegm (all symptoms/day), albuterol use (puffs/day)

BDP users had larger improvement in FEF_25–75%

(% predicted), CV, CV-VC, phlegm and albuterol use

Tunon-de-Lara, 2007¹⁷

Open, parallel-group

84 days

Patients with mild or moderate asthma

BDP 400 μg/d via HFA-pMDI

(n = 11 PP)

Medium dose

FP 500 μg/d via Diskus

(n = 14 PP)

Medium dose

FEV₁, FVC, SVC, SVC-FVC, FEV₁/FVC, FEV₁/LCV, FEF_50% and FEF_25–75% (all % predicted)

None

Van Aalderen, 2007¹⁸

Double-blind, double-dummy, parallel-group

6 weeks

Patients (5–12 years) with asthma dx ≥ 3 months from 6 sites

BDP 200 μg/d via HFA-pMDI

(n = 139 ITT)

Low dose

FP 200 μg/d via CFC-pMDI

(n = 140 ITT)

Low dose

AM PEF, PM PEF, FEV₁, FVC, FEF_25–75% (all % predicted), symptom-free days (%), nights without sleep disturbance (%), β₂-agonist therapy,mean (puffs/day)

Noninferior: lower CL > −5

(% predicted) for AM PEF;

FP users had greater improvement in FEF_25–75% (% predicted)

Bateman, 2008¹⁹

Open-label, parallel-group

24 weeks

Outpatient adults and adolescents (12–75 years) with asthma in Europe

CIC 640 μg/d via HFA-pMDI

(n = 255 ITT)

High dose

FP 660 μg/d via HFA-pMDI

(n = 273 ITT)

High dose

FEV₁ (mL), FVC (L), PEF (L/min), AM PEF (L/min), asthma symptom score, rescue medication use (puffs/day)

Absolute measures at end of treatment: Asthma symptom-free days, rescue medication-free days, asthma symptom and rescue medication-free days

Noninferior: lower CL above −200 mL for FEV₁; Noninferior: lower CL above −0.2 L for FVC; Noninferior: lower CL above -25 L/min for PEF and AM PEF

Boulet, 2007²⁰

Open-label, parallel-group

12 weeks

Adult and adolescent (12–75 years) patients with asthma from 59 Tx centers

CIC 320 μg/d via MDI

(n = 233 ITT)

Medium dose

FP 400 μg/d via DPI

(n = 239 ITT)

Medium dose

FEV₁ (mL), FEV₁ (% predicted), FVC (L), SVC (L), AM PEF (L/min), PM PEF (L/min), daytime asthma symptom score, total asthma symptom score, rescue medication use (puffs/day)

Noninferior: lower CL above

−200 mL for FEV₁;

Noninferior: lower CL above

−0.2 L for FVC;

Noninferior: lower CL above

−25 L/min for AM PEF and PM PEF

Buhl, 2006²¹

Multicenter, double-blind, double-dummy, parallel-group

12 weeks

Adult and adolescent (12–75 years) patients with asthma from 57 Tx centers

CIC 160 μg/d

(n = 266 ITT)

Low dose

FP 176 μg/d via HFA-pMDI

(n = 263 ITT)

Low dose

FEV₁ (L), FVC (L), AM PEF (L/min), daytime symptom score, night-time symptom score, total asthma symptom score (day + night score), rescue medication use (puffs/day)

Noninferior: lower CL above -0.2 L for FEV₁ and FVC;

Noninferior: lower CL above -25 L/min for AM PEF

Cohen, 2011⁴

Double-blind, double-dummy, parallel-group

65 days

Adult patients with asthma (18–60 years) recruited from outpatient clinics of pulmonology departments in the Netherlands

CIC 160 μg/d via HFA-pMDI

(n = 19)

Low dose

FP 200 μg/d via HFA-pMDI

(n = 18)

Low dose

FEV₁ (% predicted), FVC (L), SVC (L), FVC/SVC (L), FEF_50% (L/s), FEF_25–75% (% predicted)

FP users had greater improvement in FEV₁ and

FEF_25–75% (% predicted)

Dahl, 2010²²

Double-blind, double-dummy, 2-arm, parallel-group

24 weeks

Adult and adolescent patients (12–75 years) with mild to moderate asthma from 48 centers internationally

CIC 80 μg/d via HFA-pMDI

(n = 240 ITT)

Low dose

FP 200 μg/d via HFA-pMDI

(n = 240 ITT)

Low dose

FEV₁ (L), FVC (L), AM PEF (L/min)

Absolute measures at end of treatment: Days with asthma control (%), asthma exacerbations requiring Tx (%)

Noninferior: lower CL above -0.2 L for FEV₁ and FVC;

Noninferior: lower CL above -25 L/min for AM PEF

Lee, 2004²³

Double-blind, double-dummy, crossover

4 weeks per Tx

Non-smoking patients with mild-to-moderate persistent asthma

CIC 400 μg/d via HFA-pMDI

(n = 19)

High dose

FP 500 μg/d via HFA-pMDI

(n = 19)

Medium dose

NO (ppb), FEV₁ (L), FEV₁ (% predicted), FEF_25–75% (L/s), FEF_25–75% (% predicted), methacholine PD₂₀ (mg/ml), AM PEF (L/min), PM PEF (L/min), NO (ppb), AM and PM asthma symptom score, AM and PM rescue medication use (puffs/day)

None

Lee, 2005²⁴

Double-blind, double-dummy, crossover

4 weeks per Tx

Adult patients (mean age 47 years) with moderate, persistent asthma stable for 3 months

CIC 1600 μg/d via HFA-pMDI

(n = 14)

High dose

FP 2000 μg/d via HFA-pMDI

(n = 14)

High dose

Absolute measures at end of treatment: FEV₁ (L), FEV₁ (% predicted), FEF_25–75% (L/s), FEF_25–75% (% predicted), AM PEF (L/min), PM PEF (L/min), AM and PM asthma symptom score, AM and PM rescue meds (puffs/d), exhaled nitric oxide (ppb), methacholine PC₂₀ (mg/mL)

None

Magnussen, 2007²⁵

Double-blind, double-dummy, 3-arm, parallel-group

12 weeks

Patients at least 12 years of age with asthma from 91 sites

CIC 80 μg/d via HFA-pMDI

(n = 278 ITT)

Low dose

FP 178 μg/d via HFA-pMDI

(n = 259 ITT)

Low dose

FEV₁ (mL), FVC (L), PEF (L/min), asthma symptom score, daytime and night-time symptom score, rescue medication use (puffs/day)

Noninferior: lower CL above -200 mL for FEV₁;

Noninferior: limit NR for FVC and PEF

CIC 160 μg/d via HFA-pMDI

(n = 270 ITT)

Low dose

FP 178 μg/d via HFA-pMDI

(n = 259 ITT)

Low dose

FEV₁ (mL), FVC (L), PEF (L/min), asthma symptom score, daytime and night-time symptom score, rescue medication use (puffs/day)

Noninferior: lower CL above -200 mL for FEV₁;

Noninferior: limit NR for FVC and PEF

Pedersen, 2006²⁶

Multicenter, double-blind, double-dummy, 2-arm, parallel-group

12 weeks

Children (6–15 years) with asthma from 51 sites

CIC 160 μg/d via HFA-pMDI

(n = 254 ITT)

Low dose

FP 178 μg/d via HFA-pMDI

(n = 257 ITT)

Low dose

FEV₁ (L), PEF (L/min), AM PEF (L/min), PM PEF (L/min), asthma symptom score sum, asthma symptom free days, rescue medication-free days

Noninferior: lower CL greater than −0.1 L for FEV₁;

Not noninferior: lower CL less than −12.5 L/min for PEF, AM PEF and PM PEF

Pedersen, 2009²⁷

Double-blind, double-dummy, 3-arm, parallel-group

12 weeks

Children (6–11 years) with asthma from 50 international centers

CIC 80 μg/d via HFA-pMDI

(n = 234 ITT)

Low dose

FP 178 μg/d via HFA-pMDI

(n = 245 ITT)

Low dose

FEV₁ (L), AM PEF (L/min), asthma symptom score sum, rescue medication use

Absolute measures at end of treatment: Asthma exacerbations (%)

Noninferior: lower CL greater than −0.1 L for FEV₁;

Not noninferior: lower CL less than −12.5 L/min for AM PEF; Noninferior: upper CL less than 0.30 for asthma symptom score sum

CIC 160 μg/d via HFA-pMDI

(n = 232 ITT)

Low dose

FP 178 μg/d via HFA-pMDI

(n = 245 ITT)

Low dose

Noninferior: lower CL greater than −0.1 L for FEV₁;

Noninferior: lower CL greater than −12.5 L/min for AM PEF; Noninferior: upper CL less than 0.30 for asthma symptom score sum

Van der Molen, 2010²⁸

Multicenter, parallel-group (series of 3 studies)

12–24 weeks

Health patients with asthma? aged 12–75 years

CIC 320 μg/d via pMDI

(n = 224 ITT)

Medium dose

FP 400 μg/d via DPI

(n = 228 ITT)

Medium dose

CIC 640 μg/d via pMDI

(n = 244 ITT)

High dose

FP 750 μg/d via pMDI

(n = 254 ITT)

High dose

CIC 640 μg/d via pMDI

(n = 250 ITT)

High dose

FP 1000 μg/d via pMDI

(n = 237 ITT)

High dose

Fowler, 2002²⁹

Double-blind, double-dummy, parallel-group

8 weeks

Patients with asthma aged 16–70 years

BDP 400 μg/d via HFA-pMDI

(n = 20)

Medium dose

FP/SAL 200/100 μg/d via DPI

(n = 19)

Low dose

Absolute measures at end of treatment: Methacholine PD₂₀ (μg), FEV₁ (L), FEV₁ (% predicted), FEF_25–75% (L/s), FEF_25–75% (% predicted), AM PEF (L/min), PM PEF (L/min), tidal exhaled NO (ppb), symptom score, reliever use (puffs/d)

FP/SAL users had higher post-study methacholine PD₂₀, FEV₁ (L), FEV₁ (% predicted), post-study AM/PM PEF

Papi, 2007³⁰

Double-blind, 2-arm parallel-group

12 weeks

Patients with asthma aged 18–65 years from 12 outpatient respiratory clinics in Europe

BDP-F 400/24 μg/d via pMDI

(n = 115 ITT)

Medium dose

FP/SAL 500/100 μg/d via pMDI

(n = 113 ITT)

Medium dose

AM pre-dose PEF, AM PEF and PM PEF (all L/min), FEV₁ (L), FVC (L),

Absolute measures at end of treatment:

Daytime and night-time symptom score, symptom-free days (%), day time use of rescue medication (puffs)

Noninferior: lower CL above -20 L/min for AM pre-dose PEF; BDP-F users had greater improvement in FVC

Papi, 2012³¹

Prospective, controlled, 2-arm parallel-group

24 weeks

Patients with asthma aged 18–65 years from 67 respiratory clinics in Europe

BDP-F 400/24 μg/d via pMDI

(n = 206 ITT)

Medium dose

FP/SAL 500/100 μg/d via Diskus DPI

(n = 216 ITT)

Medium dose

Absolute measures at end of treatment: AM PEF (L/min), FEV₁ (L), FEV₁ (% predicted), PEF (L/min), PEF (% predicted), daytime and night-time symptom score, symptom-free days (%), patients with controlled asthma, asthma exacerbations and severe asthma exacerbations (all %)

Equivalent: CI falls within − 20 to +20 L/min for AM PEF

Scichilone, 2010³²

Double-blind, double-dummy, parallel-group

12 weeks

Adult patients with asthma (18–50 years) in Italy

BDP-F 400/24 μg/d via

HFA-pMDI

(n = 15)

Medium dose

FCS 500/100 μg/d via pMDI

(n = 15)

Medium dose

Absolute measures at end of treatment:

Pre-dose FEV₁ (L), FEF_25–75% (L/s), PD₂₀ FEV₁ methacholine (μg)

None