Chen 2008.

Methods	RCT using simple random allocation to intervention and control groups
Participants	68 childhood cancer patients, receiving phosphocreatine or control treatment of a combination of vitamin C, ATP, vitamin E, and coenzyme Q10. Included participants had anthracycline‐related cardiotoxicity based on cardiac enzymes (CK, CK‐MB, LDH1, alphaHBDH, troponin I, hsCRP), ECG and/or echocardiogram. Median (range) age of the phosphocreatine group was 5 (1 to 15) years; 15 of 35 were males. Age and gender of the control group were not mentioned. Median time since cancer diagnosis was not mentioned. Participants had a diagnosis of acute lymphatic leukaemia or acute myeloid leukaemia. For both groups information on (previous) cardiotoxic cancer treatment (cumulative anthracycline dose, cardiac radiotherapy and dose, and cardioprotective interventions) was not mentioned. Other cardiovascular comorbidities and treatments were also not mentioned. At the start of the study, distribution of abnormalities in cardiac symptoms and signs in the treatment group (n = 35) was: cardiac symptoms 18, abnormal cardiac enzymes 28, abnormal troponin I 7, abnormal ECG 20, and abnormal echocardiogram 0. Mean (SD) hsCRP in the treatment group was 8.79 (1.36) mg/L. For the control group (n = 33) this distribution was: cardiac symptoms 16, abnormal cardiac enzymes 25, abnormal troponin I 7, abnormal ECG 18, and abnormal echocardiogram 0. Mean (SD) hsCRP in the control group was 7.88 (2.08) mg/L. Time since diagnosis of cardiotoxicity was not mentioned
Interventions	Phosphocreatine 1 g intravenously over 30 to 40 minutes once to twice per day (n = 35) or a combination treatment of vitamin C 150 mg/kg and ATP 20 mg into 5% glucose 100 ml intravenously once per day, oral vitamin E 50 mg once per day, and oral coenzyme Q10 (ubidecarenone) 10 mg 3 times per day. All treatment durations were 14 days
Outcomes	Overall survival. Mortality due to heart failure (no definitions provided). Occurrence of adverse events (no definition provided). Change in cardiac function (normal/abnormal echocardiography, change in hsCRP, normal/abnormal ECG, normal/abnormal cardiac enzymes (CK, CK‐MB, LDH1, alphaHBDH, troponin I, and hsCRP), postintervention levels of CK, CK‐MB, LDH1, alphaHBDH, and troponin I. No definitions were provided)
Notes	The abstract (in English) mentions "retrospectively assessed". However, we think the study is an RCT, because there is a statement in the methods section (in Chinese) that "all patients have entered the clinical trial with simple random allocation to treatment and control groups." Duration of follow‐up was not mentioned, but it seems that it was 15 days for the assessment of cardiac function, since that was done at the beginning and one day after the intervention. For clinical outcomes this was unclear. There was no loss to follow‐up
Risk of bias
Bias	Authors' judgement	Support for judgement
Blinding of participants?	High risk	Blinding of participants was not mentioned but seemed inadequate or very unlikely since the intervention and control treatment had different routes of administration
Blinding of personnel?	High risk	Blinding of personnel was not mentioned but seemed inadequate or very unlikely since the intervention and control treatment had different routes of administration
Blinding of outcome assessors? Mortality due to heart failure	Unclear risk	Blinding of outcome assessors was not mentioned
Blinding of outcome assessors? Occurrence of adverse events and tolerability (as defined by authors)	Unclear risk	Blinding of outcome assessors was not mentioned
Blinding of outcome assessors? Change in cardiac function measured by a diagnostic test (as defined by authors)	Unclear risk	Blinding of outcome assessors was not mentioned
Completeness of follow‐up Overall survival	Low risk	Outcome could be abstracted for all participants
Completeness of follow‐up Mortality due to heart failure	Low risk	Outcome could be abstracted for all participants
Completeness of follow‐up Occurrence of adverse events and tolerability (as defined by authors)	Low risk	Outcome was provided for all participants
Completeness of follow‐up Change in cardiac function measured by a diagnostic test (as defined by authors)	Low risk	For echocardiography (normal/abnormal) change in outcome was provided for all participants
Completeness of follow‐up Change in cardiac function measured by a diagnostic test (as defined by authors)	Low risk	For 1 biomarker (hsCRP) change in outcome was provided for all participants
Intention‐to‐treat‐analysis? Overall survival	Low risk	Allocation was provided for the reported outcome
Intention‐to‐treat‐analysis? Mortality due to heart failure	Low risk	Allocation was provided for the reported outcome
Intention‐to‐treat‐analysis? Occurrence of adverse events and tolerability (as defined by authors)	Low risk	Allocation was provided for the reported outcome
Intention‐to‐treat‐analysis? Change in cardiac function measured by a diagnostic test (as defined by authors)	Low risk	For echocardiography (normal/abnormal) treatment allocation was provided
Intention‐to‐treat‐analysis? Change in cardiac function measured by a diagnostic test (as defined by authors)	Low risk	For the biomarker (hsCRP) treatment allocation was provided
Free of selective reporting?	Unclear risk	We found no published protocol in which the reported outcomes and analyses were prespecified
Free of other bias?	High risk	The baseline characteristics were not fully described. For example, there was no data about the gender and age distribution of the control group. We do not know what type of anthracycline and what doses of medications were used in each group, and we have no information on whether radiation therapy was given. We are therefore uncertain whether the intervention and control groups were comparable/similar at baseline. We are uncertain whether co‐interventions were different between the intervention and control groups
Random sequence generation?	Unclear risk	No description of sequence generation
Allocation concealment?	Unclear risk	No description of allocation concealment