Sildenafil for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: A Phase I/II Randomized Clinical Trial, SILDAT-TAHA6 Trial

Background. Previous animal studies have shown a protective effect of 5-phosphodiesterase inhibitors on cancer therapeutics-related cardiac dysfunction (CTRCD) of anthracyclines. Aim. The aim of this study was to evaluate the clinical effect of sildenafil on the primary prevention of CTRCD in human. Materials and Methods. In this randomized double-blind clinical trial, the primary end point was efficacy in preventing the reduction of left ventricular ejection fraction (LVEF). The intervention group patients received sildenafil at a dose of 25 milligrams twice a day before starting the chemotherapeutic regimen, and the control group received placebo. All the patients at baseline and after the 6-month follow-up underwent 4D and speckle-tracking echocardiography and cardiac MRI, accompanied by hs-troponin I and NT-Pro-BNP measurement. Results. Sixty patients were enrolled in this study, and data from 52 patients (24 patients in the intervention group and 28 patients in the control group) were used in the final analysis. Our findings showed that in the intervention and control groups, LVEF was dropped from 61.28 ± 7.36 to 51.57 ± 7.67 (difference (D) = −9.71 ± 11.95, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>p</a:mi> <a:mo>=</a:mo> <a:mn>0.003</a:mn> </a:math> ) and from 57.9 ± 7.29 to 50.2 ± 7.02% (D = −7.7 ± 5.93; <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>p</c:mi> <c:mo>=</c:mo> <c:mn>0.001</c:mn> </c:math> ), respectively (between-group difference = −2.01%, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>p</e:mi> <e:mo>=</e:mo> <e:mn>0.26</e:mn> </e:math> ). CTRCD was detected in 11 patients in the control group (42.8%) and 10 in the intervention group (41.6%, <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>p</g:mi> <g:mo>=</g:mo> <g:mn>0.51</g:mn> </g:math> ). Conclusion. Consumption of sildenafil for primary prevention of anthracycline-induced cardiac toxicity seems to be unbeneficial. This trial is registered with IRCT20180506039554N1.