Rajanandh 2015.

Methods	Study design: RCT Study grouping: parallel group Open label: yes Cluster RCT: no
Participants	Baseline characteristics LAMA add‐on Number randomised: 88 N umber completed: 72 Mean age (SD): 37.4 (13.6) years % Male: 52.8 % Predicted FEV1 (SE): 66.1 (6.4) % White: NR Duration of asthma (SD): 5.8 (8.7) years LABA add‐on N umber randomised: 88 Number completed: 68 Mean age (SD): 38.4 (14.9) years % Male: 55.4 % Predicted FEV1 (SE): 66.2 (8.3) % White: NR Duration of asthma (SD): 6.6 (6.7) years Inclusion criteria: aged 18‐60 years, both men and women diagnosed clinically with mild‐to‐moderate persistent asthma, with an improvement in FEV1 > 12% after bronchodilator inhalation. Written informed consent was obtained from all participants prior to the study Exclusion criteria: participants with clinically significant renal, respiratory (other than asthma) cardiac, gastrointestinal, hepatic, endocrine disorders, haematological disorders, cancer or any other concurrent illness; participants who had undergone major surgery; unresolved upper respiratory tract infection within past 3 weeks of the pre‐study visit; corticosteroids during the month prior to the study; known or suspected hypersensitivity to study therapy or excipients; unwilling to give informed consent; pregnant and lactating women
Interventions	Intervention characteristics LAMA add‐on ICS type/dose: budesonide 400 mcg Add‐on type/dose: tiotropium 18 mcg once daily Co‐medications: participants were excluded if they had taken any oral, inhaled or parenteral forms of steroid during the month before the study Type of inhaler: HandiHaler Duration of treatment: 6 months LABA add‐on ICS type/dose: budesonide 400 mcg Add‐on type/dose: formoterol 12 mcg twice daily Co‐medications: people were excluded if they had taken any oral, inhaled or parenteral forms of corticosteroid during the month before the study Type of inhaler: dry powder inhaler Duration of treatment: 6 months
Outcomes	Continuous Trough FEV1 (L) ‐ could not be meta‐analysed Rescue medication (puffs/day) ‐ not a pre‐specified outcome of this review Health‐related quality of life on the St George's Respiratory Questionnaire ‐ could not be meta‐analysed Asthma symptom scores ‐ not a pre‐specified outcome of this review No dichotomous outcomes were listed
Identification	Sponsorship source: SRM University Country: India Setting: Department of Pulmonary Medicine, SRM Medical College Hospital and Research Centre Registration ID: CTRI/2012/08/002915 Authors name: Muhasaparur G. Rajanandh Institution: SRM College of Pharmacy, Tamil Nadu, India Email: mgrpharm@gmail.com Address: SRM College of Pharmacy, SRM University, Kattankulathur, Chennai, Kancheepuram, TAMIL NADU603 203, India
Notes	Contacted author November 2014 ‐ awaiting full publication
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A randomisation list was generated using Random allocation software, version 1.0
Allocation concealment (selection bias)	Low risk	"Concealment of optimization codes was done by serially numbered, opaque envelope model" Envelopes were sealed (CTRI website)
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label. No description of measures taken to blind outcome assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	18% dropped out of tiotropium group and 19% dropped out of formoterol groups. "Per protocol analysis was performed"
Selective reporting (reporting bias)	High risk	The main trial was retrospectively registered (CTRI/2012/08/002915). All 4 outcomes were reported in the paper, although could not in sufficient detail to allow meta‐analysis (i.e. without group means and variance, or with details of a group comparison with level of statistical significance)
Other bias	Low risk	None noted

ACQ: Asthma Control Questionnaire; AE: adverse event; AQLQ: Asthma Quality of Life Questionnaire; COPD: chronic obstructive pulmonary disease; ED: emergency department; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity; HFA: hydrofluoroalkane; ICS: inhaled corticosteroids; ITT: intention to treat; L: litres; LABA: long‐acting beta₂‐agonists; LAMA: long‐acting muscarinic antagonists; mcg: micrograms; MDI: metered dose inhaler; min: minute; N/A: not available; NR: not reported; OCS: oral corticosteroids; PC20: histamine provocative concentration causing a 20% drop in FEV₁; PEF: peak expiratory flow; RCT: randomised controlled trial; SAE: serious adverse event; SD: standard deviation; SE: standard error; TB: tuberculosis.