Grazioli 1992

Methods	A multicenter randomized controlled clinical trial in patients with heart failure to evaluate the effects of CrP in addition to conventional therapy. Patients were treated with CrP or placebo i.v. for 2 weeks, followed by CrP or placebo i.m. for 1 month. Clinical symptoms and NYHA classes, electrocardiographic signs of ischemia, and use of sublingual nitroglycerin were evaluated. There was no follow‐up after stopping treatment with CrP.
Participants	1007 patients hospitalised for heart failure; 508 patients were randomized to receive CrP and 499 patients were randomized to receive placebo.
Interventions	One gram CrP i.v. daily added to conventional treatment or no added treatment for two weeks (acute treatment) followed by 500 mg CrP i.m. daily or no added treatment for 1 month.
Outcomes	Outcomes on death, total myocardial infarction, hospitalization for heart failure, or changes in blood pressure were not reported. Ejection fraction at rest and at work did not change. The other outcomes reported were clinical symptoms of heart failure and angina pectoris with a 4‐point score, use of sublingual nitrogen, and rhythm, type and number of premature beats, ST segment, T wave, and atrioventricular conduction on the ECG. On dyspnoea a significant difference was reported after the 45‐day treatment measured with a four point scale: in the intervention group 7% reported moderate to severe dyspnoea vs 23% in the control group (p < 0.001) The number of patients in NYHA classes III and IV decreased significantly more in the CrP group (9%) than in the control group (24%). The clinical symptoms of heart failure, the main signs of ischaemia and a decrease in ventricular premature beats in the intervention group of 68% vs. 57% in the control group after 15 days (p < 0.05).
Notes	Current Therapeutic Research ‐ Clinical and Experimental. 52(2)(pp 271‐280), 1992.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "According to a randomization code". So sequence generation was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "According to a randomization code".
Blinding (performance bias and detection bias) All outcomes	High risk	No placebo used.
Incomplete outcome data (attrition bias) All outcomes	High risk	No reports on withdrawal, no missing data.
Selective reporting (reporting bias)	High risk	All outcomes mentioned in methods are reported. Nonsignificant outcomes only described as: "no statistically significant differences". No absolute numbers.
Other bias	High risk	(Side) effect attribution is difficult because simultaneous usage of standard therapy, e.g. "no side effects related to CrP treatment were reported". Possible differential diagnostic activity, because there was no blinding.