Mereles 2006.

Methods	Study design: RCT Study grouping: Parallel group
Participants	Baseline characteristics Exercise Number enrolled: 15 Gender (male/female): 5/10 Age (years): 47 (12) Type of PH: PAH n = 13, CTEPH n = 2 Haemodynamics: PASP (mmHG, Echo): 61 (18) Haemodynamics: CI (L/min/m2, Echo): Haemodynamics: mPAP (mmHG, RHC): 49.5 (17.6) Haemodynamics: PVR (Dyne.s/cm5, RHC): 968.7 (444.1) Height (cm): 171 (11) Weight (kg): 75 (13) Medications (single/double/triple): 6/5/4 NYHA, WHO Functional Class (I/II/III/IV): 0/2/12/1 Control Number enrolled: 15 Gender (male/female): 5/10 Age (years) 53 (14) Type of PH: PAH n = 11, CTEPH n = 4 Haemodynamics: PASP (mmHG, Echo): 61 (18) Haemodynamics: CI (L/min/m2, Echo): Haemodynamics: mPAP (mmHG, RHC): 49.6 (12.3) Haemodynamics: PVR (Dyne.s/cm5, RHC): 901.8 (358.0) Height (cm): 166 (5) Weight (kg): 78 (18) Medications (single/double/triple): 7/5/3 NYHA, WHO Functional Class (I/II/III/IV): 0/4/10/1 Included criteria: people with severe chronic PH who were stable and compensated under optimised medical therapy (such as endothelin antagonists, iloprost, sildenafil, calcium channel blockers, anti‐coagulants, diuretics, and supplemental oxygen) for at least 3 months before entering the study were invited to participate. Additional inclusion criteria were age 18‐75 years, WHO functional class II to IV. Excluded criteria: no recent syncope, and no skeletal or muscle abnormalities prohibiting participation in an exercise programme Pretreatment: Nil evident
Interventions	Intervention characteristics Exercise Setting: 3 weeks inpatient followed by 12 weeks outpatient, unsupervised training Components: exercise training (see below), mental training to improve perception of physical abilities and limits to keep physical exercise safe even in demanding situations, dumbbell training of single muscle groups with low weights (500‐1000 g) and 30 min of respiratory training, including stretching, breathing techniques such as pursed lip breathing, body perception, yoga, and strengthening of respiratory muscles Training dose: frequency: inpatient: walking and cycling 7 d/week, resistance ex and respiratory training 5 d/week. Outpatient: cycling 5 x/week, walk twice a week, respiratory training and resistance ex second daily Intervention (mode): interval bicycle ergometer training, walking, respiratory training, resistance training Training dose: duration: 10‐25 min cycle ergometer, 60 min walking, 30 min resistance training, 30 min respiratory training Training dose: intensity: cycle ergometer; 60%‐80% of HR on CPET. HR maintained < 120 bpm, oxygen saturation > 85% Control Intervention (mode): "Patients in the control group received a common rehabilitation program based on healthy nutrition, physical therapy such as massages, inhalation, counselling, and muscular relaxation without exercise and respiratory training but were allowed to perform daily activity as usual. All patients were advised to avoid heavy exercise" Training dose: duration: 0 (I) 0 (O) Training dose: intensity: 0 (I) 0 (O) 10 of 15 participants entered the exercise training arm at the end of the study
Outcomes	6MWD VO2peak Wpeak Morbidity ‐ adverse events Disease progression Precluded from training Anaerobic threshold HRQoL (SF‐36): Physical functioning HRQoL (SF‐36): Role physical HRQoL (SF36): Bodily pain HRQoL (SF‐36): General health HRQoL (SF‐36): Vitality HRQoL (SF‐36): Social function HRQoL (SF‐36): Role emotional HRQoL (SF‐36): Mental health HRQoL:Physical Summary score (SF36) HRQoL:Mental Summary score (SF36) HRQol (CAMPHOR): QoL NYHA Class Discontinued training
Identification	Sponsorship source: this study was funded by a grant from the German Pulmonary Hypertension Group, Pulmonale Hypertonie e.V., Rheinstetten, Germany. Country: Germany Setting: inpatient rehabilitation Comments: Author's name: Derliz Mereles Institution: University Hospital Heidelberg Email: ekkehard_gruenig@med.uni‐heidelberg.de Address: Department of Cardiology and Pneumology, University Hospital Heidelberg, INF 410, D‐69120 Heidelberg
Notes	Adverse Outcomes Authors report that all participants tolerated training and had no adverse events during training and no progression of the disease as defined by progression of symptoms, PH or right heart failure. Two participants perceived a short episode of dizziness without fainting immediately after bicycle ergometer training. In 1 participant, oxygen saturation dropped from 88% to 74% during exercise, although the training was performed with an oxygen mask. Continuous Outcomes 6MWD is reported as a change from baseline at the post‐inpatient and post‐outpatient time points
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: participants were randomly assigned to either a primary training group or a sedentary control group using a permuted block randomization procedure
Allocation concealment (selection bias)	Unclear risk	Comment: there is no comment regarding allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: unable to blind participants and personnel due to nature of intervention
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The completed questionnaire at baseline was compared with the results after 15 weeks by investigators who were blinded to the patients’ clinical data and group assignment. To avoid bias as far as possible in this study, all measurements and/or offline readings were performed by investigators who were blinded to patient data and group assignment."
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts reported
Selective reporting (reporting bias)	Low risk	The protocol was not registered or published however the outcome reporting is comprehensive.
Other bias	High risk	Comment: No CONSORT diagram so not possible to tell how many people were assessed in order to recruit the sample.