Mittal 2017.

Methods	Study design: RCT Centres: 1, Cardiology Outpatient Department and HTN clinic of Postgraduate Institute of Medical Education and Research, India Start of enrolment: 15 November 2009 (from clinical trial registry) End of enrolment: not reported for pilot study, full study ongoing Follow‐up: 12 weeks Run‐in period: 2 weeks placebo run in (beta‐blocker withdrawn but co‐existing therapies were continued)
Participants	Inclusion criteria: "18 years and above, had New York Heart Association (NYHA) functional Class II–III of at least 4 weeks' duration, LVEF ≥ 50% in a nondilated LV (LV end­diastolic volume < 97 ml/m measured by echocardiography), echocardiographic evidence of LV diastolic dysfunction, and were willing to give written informed consent." Exclusion criteria: "They were excluded if: (1) Clinically unstable as defined by any change in diuretic dose in the month before enrollment, (2) significant valvular heart disease, pericardial disease, hypertrophic or restrictive cardiomyopathy, (3) unstable angina or MI within past 4 weeks, (4) any previous LVEF below 40%, (5) any contraindication to metoprolol use, (6) patients already on beta blockers which cannot be withdrawn, (7) current participation (including prior 30 days) in any other therapeutic trial, and (8) any condition that, in the opinion of investigator, may prevent the participant from adhering to the trial protocol." Randomised (N): 40 (20 intervention, 20 control) Withdrawn (N): for reasons other than death 0 Lost to follow‐up (N): 6 (3 intervention, 3 control) Analysed (N): 40 (20 intervention, 20 control) Age (years, mean, SD): intervention: 55.2, 7.1; control: 57.2, 9.8 Sex (% men): intervention: 45; control: 50 Ethnicity (%): not reported Systolic blood pressure not reported Heart rate not reported BMI not reported Serum creatinine not reported B‐type natriuretic peptide not reported NT pro B‐type natriuretic peptide (pg/mL, median (IQR)): intervention: 238.2 (107.7‐2230.2); control: 227.6 (58.3‐3645) LVEF (%, mean, SD): intervention: 62.9, 6.2; control: 62.1, 6.57 NYHA class I (%): 0 NYHA class II (%): intervention: 55; control: 65 NYHA class III (%): intervention: 45; control: 35 NYHA class IV (%): 0 Hypertension (%): not reported Diabetes (%): not reported Atrial fibrillation (%): not reported Hospitalisation for heart failure: not reported Coronary heart disease (%): not reported Stroke (%): not reported Diuretic (%); intervention: 35; control: 40 Digoxin (%): not reported Beta‐blocker (%): intervention: 40; control: 45 ACEI (%): intervention: 15; control: 60 ARB (%): intervention: 15; control: 15 MRA (%): not reported
Interventions	Intervention: metoprolol succinate, 25 mg. "A dose upward titration protocol with monitoring of blood pressure and heart rate (target blood pressure and heart rate as 120/80 mm Hg and 60 beats/min, respectively) was implemented for dose increments up to a maximum dose of 100 mg once daily. For patients not tolerating increased titration of drug, temporary reduction in dosage was done and decision on further escalation made on individual basis by the treating cardiologist." Comparator: placebo Concomitant medication: "During the study, calcium channel blockers were added in three patients (one in placebo and two in metoprolol group) due to high blood pressure records." coexisting therapies were continued
Outcomes	Planned: unable to assess Reported: primary: NYHA class. Secondary: exercise capacity, diastolic dysfunction, change in LV wall thickness, LV mass, NT‐proBNP, PICP, QoL (SF‐36), adverse events, withdrawals
Notes	published results after our search date, identified via search for clinical trial registry number: CTRI/2010/091/000438 which was retrieved by search of the WHO ICTRP register Emailed investigators to ask when completion of full trial is anticipated. Response confirmed that full trial was not conducted.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"block randomised" but no further details
Allocation concealment (selection bias)	Low risk	"Randomization and allocation sequence generation were done by investigators not directly involved in the evaluation of outcomes" From clinical trial registry: "sequentially numbered, sealed, opaque envelopes"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"double‐blind" From clinical trial registry entry: "participant and outcome assessor blinded" Unclear whether personnel was blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"To avoid interobserver variability, all the echocardiographic parameters were evaluated by a single cardiologist who was blinded to study medication and the order of assessment." From clinical trial registry entry: "participant and outcome assessor blinded"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	pilot study ‐ full study ongoing same numbers lost to follow‐up in both arms ITT and per‐protocol analysis used
Selective reporting (reporting bias)	Unclear risk	unable to assess due to lack of published protocol and uncertainty over trial registration date
Other bias	Low risk	"The study was supported by Postgraduate Institute of Medical Education and Research, Chandigarh, India." "There are no conflicts of interest" Results from pilot study only so far.