Kuethe 2006

Methods	In a double‐blind, placebo‐controlled and crossover‐designed study, 20 patients with HF received creatine daily vs. placebo per os for 6 weeks and were crossed over for the following 6 weeks. Peak VO2, VO2 at the anaerobic threshold (VO2AT), EF, distance in 6‐minute‐walktest (6 min W), and muscle strength (Modified Sphygmomanometer (MS)) were determined at baseline, after 6, and after 12 weeks. Dyspnoea after 6‐minute‐walk‐test was measured using the Borg Scale. Quality of live was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ). There was no follow‐up period after withdrawal of creatine treatment.
Participants	Twenty patients with a history of congestive heart failure of more than 6 months, NYHA II and III, and a peak oxygen uptake (peak VO2) of less than 20 ml/min/kg.
Interventions	4 x 5 g creatine daily vs. placebo per os for 6 weeks. For the following 6 weeks the patients were crossed over to receive creatine or placebo.
Outcomes	Outcomes on death, total myocardial infarction, hospitalization for heart failure, or changes in blood pressure were not reported. Ejection fraction: no significant change in ejection fraction compared to baseline in the creatine (29.8 ± 8.6%) and the placebo group (28.7 ± 7.5%) after six weeks. Other outcomes: 13 of 20 patients finished the study. A significant increase in body weight (85.9 ± 10.3 kg) compared to baseline (83.6 ± 10.6 kg) and placebo (84.3 ± 10.2 kg) and muscle strength (112,5 ± 14,8 mm Hg) compared to baseline (96.8 ± 26.5 mmHg) and placebo (88,3 ± 11,9 mmHg) after 6 weeks of oral supplementation of creatine (p < 0.05). However, there was no significant change in peak VO2, VO2AT, ventricular end diastolic diameter, walking distance, Borg Scale levels of dyspnoea, and quality of life assessment.
Notes	Pharmazie. 61(3)(pp 218‐222), 2006.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Only mentioned "double‐blind placebo‐controlled and crossover designed study". So randomization method is not mentioned.
Allocation concealment (selection bias)	Unclear risk	Only mentioned "double‐blind placebo‐controlled and crossover designed study".
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "double‐blind", not further detailed.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "13 of 20 patients finished the study." Reasons given. Not related to the treatment (evenly divided between the creatine and placebo group). Reasons were: 1 a cold, 1 a death, 1 newly diagnosed breast cancer, 1 acute decompensation, 3 stopped without giving reasons.
Selective reporting (reporting bias)	Low risk	All end points detailed.
Other bias	High risk	Cross‐over design: the measurements presented disregarding the sequence of creatine and placebo in the cross‐over regime. A washout period of four week was considered to "excluded an overlap of possible creatine effects". Small population (13). Relatively high amount of drop‐outs (7/20). Possible baseline imbalance due to different co‐medication at baseline.