Jahanian 2021.

Study characteristics
Methods	Study design: phase 3 randomised double‐blind placebo‐controlled trial with parallel assignment Number of study centres and location: single centre; Imam Khomeini Hospital in Sari, Mazandaran Province, Iran Study setting: emergency department (ED) Withdrawals: stated Date of study: September 2016 to February 2018
Participants	Number screened: 72 Number randomised: 60 Number in treatment group: 30 Number in placebo group: 30 Mean age (years): 62.9 (SD 7.3) (magnesium); 65.8 (SD 3.1) (placebo) Gender (male/female): 5/25 (magnesium); 9/21 (placebo) Diagnostic criteria: physician diagnosed Disease duration of less than 5 years (n): 20 (magnesium); 18 (placebo) Smoking history Current smokers: 16 (magnesium); 17 (placebo) Inclusion criteria: adults with known clinically diagnosed moderate COPD (FEV1/FVC < 70%, 30 < FEV1 < 50, often symptomatic with shortness of breath) with the acute attack symptoms including changes in the severity of shortness of breath, cough, and sputum volume Exclusion criteria required tracheal intubation or noninvasive ventilation on admission to ED had a history of cardiac disease were not able to cooperate or undergo spirometry and with reduced level of consciousness were pregnant had diseases that mimic the clinical features of COPD such as pneumonia, pleural or pericardial effusion, pneumothorax, heart failure, renal failure, sepsis, or a past history suggestive of asthma. use of intravenous magnesium sulfate in the past 24 hours systolic blood pressure < 100mmHg using medications that contain magnesium presence of hyperkalaemia or hypocalcaemia with ECG abnormalities respiratory rate < 16 use of magnesium hydroxide or aluminium‐magnesium hydroxide syrups during the past 24 hours.
Interventions	Intervention: intravenous infusion of magnesium sulfate (2 g in 100 mL of normal saline) over 30 minutes Placebo: intravenous infusion of 0.9% normal saline (100 mL) over 30 minutes After receiving standard treatment for COPD exacerbation: nasal‐cannula oxygen therapy (2 to 3 L/min); inhaled salbutamol and ipratropium (6 puffs every 20 minutes for a maximum of 3 times); intravenous hydrocortisone (100 mg).
Outcomes	FEV1, RR, PR, SpO2 and 0 to 10 Borg dyspnoea scale at 45 minutes and 6 hours after the commencement of intervention
Notes	Funding for studies: Clinical Research Development Unit of Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran Conflicts of interest of trial authors: declared none Clinical Trials Registry: IRCT20150315021480N8 (Iranian Registry of Clinical Trials Database)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was done using a computer‐generated random numbering system with the help of a nurse who was blinded to the study groups.
Allocation concealment (selection bias)	Low risk	Randomisation was done using a sealed envelope technique with the help of a nurse who was blinded to the study groups.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All drugs were prepared in syringes in the same size, colour, volume, and shape. The syringes were labelled as A or B by a pharmacist and were administered by a nurse. Particpants were unaware of the type of medication they were receiving.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details provided for outcome assessment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no dropouts from either arm.
Selective reporting (reporting bias)	Low risk	Trial was registered on website, all outcome measures were reported as planned. Moreover, the authors stated their willingness to share the data upon request.
Other bias	Low risk	None identified.