Table 4.

Occurrence of adverse events

Adverse Event (n [%])Avosentan 25 mg (n = 455)Avosentan 50 mg (n = 478)Placebo (n = 459)P
Avosentan 25 mg versus PlaceboAvosentan 50 mg versus Placebo
Patients with ≥1 adverse event322 (70.8)346 (72.2)309 (67.0)0.1640.325
Patients with ≥1 serious adverse event149 (32.7)145 (30.3)112 (24.3)0.0010.122
Withdrew because of adverse events89 (19.6)87 (18.2)53 (11.5)0.0010.020
Patients with symptoms of fluid overload204 (44.8)219 (45.8)141 (30.7)0.0001<0.0001
Anemia49 (10.8)64 (13.4)16 (3.5)0.0002<0.0001
    hypoglycemia20 (4.4)23 (4.8)13 (2.8)0.1390.052
    hyperkalemia16 (3.5)19 (4.0)14 (3.0)0.4070.120
    hypertension11 (2.4)12 (2.5)17 (3.7)0.2800.171
    hypotension6 (1.3)14 (2.9)4 (0.9)0.3220.047
  • Symptoms of fluid overload (see also Table 5) were taken from the reports of adverse and serious adverse events of the investigative centers and included reports of heart failure, edema, fluid overload, fluid retention, hypervolemia, dyspnea, effusions, weight increase, and rales (see Concise Methods section). Anemia, hypertension, hypotension, hyperkalemia, and hypoglycemia were not defined but were also taken from the reports of the clinical investigators. Statistics: Cochran-Mantel-Haenszel test controlling for investigative center.