OBJECTIVES: In a randomized double-blind crossover trial, we compared the efficacy of phosphodiesterase-5 (PDE-5) inhibitor tadalafil with placebo in patients of Eisenmenger Syndrome (ES). The primary end point was the change in 6-minute walk test distance (6 MWD). Secondary end points were the effect of the drug on systemic oxygen saturation (SO(2) ), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), effective pulmonary blood flow (EPBF), and World Health Organization (WHO) functional class. BACKGROUND: ES is a disorder with limited treatment options. Uncontrolled studies have shown PDE-5 inhibitors to be beneficial in patients of ES. METHODS:Twenty-eight symptomatic adult patients of ES with weight ≥30 kg in WHO class II and III were enrolled. Patients were given 40 mg of tadalafil or matching placebo for 6 weeks followed by crossover to the other drug after a washout period of 2 weeks. Assessment of WHO class, exercise capacity by 6 MWD, and various hemodynamic parameters by cardiac catheterization was done at baseline, after 6 weeks and at the end of the study. RESULTS: All patients completed the study. There was significant increase in 6 MWD following drug administration compared with baseline (404.18 ± 69.54 m vs. 357.75 ± 73.25 m, P < .001). Compared with placebo, tadalafil produced significant decrease in PVR (-7.32 ± 1.58, P < .001), resulting in significant increase in EPBF (0.12 ± 0.05, P= .03), SO(2) % (1.72 ± 0.58, P= .007), and WHO functional class (1.96 ± 0.18 vs. 2.14 ± 0.44, P= .025), with no significant change in SVR (P= NS). CONCLUSION: In this first short-term placebo-controlled trial of tadalafil in patients of ES, the drug was well tolerated and significantly improved exercise capacity, functional class, SO(2) , and pulmonary hemodynamics.
RCT Entities:
OBJECTIVES: In a randomized double-blind crossover trial, we compared the efficacy of phosphodiesterase-5 (PDE-5) inhibitor tadalafil with placebo in patients of Eisenmenger Syndrome (ES). The primary end point was the change in 6-minute walk test distance (6 MWD). Secondary end points were the effect of the drug on systemic oxygen saturation (SO(2) ), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), effective pulmonary blood flow (EPBF), and World Health Organization (WHO) functional class. BACKGROUND: ES is a disorder with limited treatment options. Uncontrolled studies have shown PDE-5 inhibitors to be beneficial in patients of ES. METHODS: Twenty-eight symptomatic adult patients of ES with weight ≥30 kg in WHO class II and III were enrolled. Patients were given 40 mg of tadalafil or matching placebo for 6 weeks followed by crossover to the other drug after a washout period of 2 weeks. Assessment of WHO class, exercise capacity by 6 MWD, and various hemodynamic parameters by cardiac catheterization was done at baseline, after 6 weeks and at the end of the study. RESULTS: All patients completed the study. There was significant increase in 6 MWD following drug administration compared with baseline (404.18 ± 69.54 m vs. 357.75 ± 73.25 m, P < .001). Compared with placebo, tadalafil produced significant decrease in PVR (-7.32 ± 1.58, P < .001), resulting in significant increase in EPBF (0.12 ± 0.05, P= .03), SO(2) % (1.72 ± 0.58, P= .007), and WHO functional class (1.96 ± 0.18 vs. 2.14 ± 0.44, P= .025), with no significant change in SVR (P= NS). CONCLUSION: In this first short-term placebo-controlled trial of tadalafil in patients of ES, the drug was well tolerated and significantly improved exercise capacity, functional class, SO(2) , and pulmonary hemodynamics.