Objective: This study evaluated the efficacy and safety of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH). Methods: This phase-3, international, randomized, multicenter (24 weeks double-blind placebo controlled period; 2-year, open-labelled extension period), add-on (patientâs current endothelin receptor antagonist therapy) study included pediatric patients aged <18 years with PAH. Patients received tadalafil 20 mg or 40 mg based on their weight (Heavy-weight: â¥40 kg; Middle-weight: â¥25â<40 kg) or placebo orally QD for 24 weeks. Primary endpoint was change from baseline in 6-minute walk (6MW) distance in patients aged â¥6 years at Week 24. Sample size was amended from 134 to â¥34 patients, due to serious recruitment challenges. Therefore, statistical significance testing was not performed between treatment groups. Results: Patient demographics and baseline characteristics (N=35; tadalafil=17; placebo=18) were comparable between treatment groups; median age was 14.2 years (6.2 to 17.9 years) and majority (71.4%, n=25) of patients were in HW cohort. Least square mean (SE) changes from baseline in 6MW distance at Week 24 was numerically greater with tadalafil versus placebo (60.48 [20.41] vs 36.60 [20.78] meters; placebo-adjusted mean difference [SD] 23.88 [29.11]). Safety of tadalafil treatment was as expected without any new safety concerns. During study period 1, two patients (1 in each group) discontinued due to investigatorâs reported clinical worsening, and no deaths were reported. Conclusions: The statistical significance testing was not performed between the treatment groups due to low sample size, however, the study results show positive trend in improvement in non invasive measurements, commonly utilized by clinicians to evaluate the disease status for children with PAH. Safety of tadalafil treatment was as expected without any new safety signals.
Statistical significance testing and p-values: Defending the indefensible? A discussion paper and position statement
