Table 3.

Total Adverse Events and Serious Adverse Events in the Two Study Groups.^*

Category	Total Adverse Events				Serious Adverse Events
	Treatment Period		Observation Period		Treatment Period		Observation Period
	Placebo	Sirolimus	Placebo	Sirolimus	Placebo	Sirolimus	Placebo	Sirolimus
	number of events
Allergy or immunologic event	13	11	1	1
Auditory or ear-related event	2	4	0	1
Blood or bone-marrow event	4	12	1	0	0	1	0	0
Cardiac arrhythmia	0	2	0	2
Cardiac event, general	12	15	3	2	0	5	0	0
Constitutional symptom	35	46	7	7
Death not related to an event	0	0	1	0	0	0	1	0
Dermatologic event	41	106	8	11
Endocrinologic event	3	2	2	0	0	0	1	0
Gastrointestinal event	181	275	12	20	1	3	0	0
Hemorrhage or bleeding event	14	17	3	1	0	0	1†	0
Hepatobiliary or pancreatic event	1	0	1	0	0	0	1	0
Infection	74	78	20	24	3	2	1	0
Lymphatic event	8	15	6	0
Metabolic event or abnormal laboratory result	26	56	1	6	0	1	0	0
Musculoskeletal or soft-tissue event	21	35	2	4	0	1	0	1
Neurologic event	27	33	4	7
Ocular or visual problem	3	8	1	2
Pain	115	130	9	13	1	7	0	0
Pulmonary or upper respiratory event	121	97	17	32	13	2	0	0
Renal or genitourinary event	8	11	0	2
Sexual or reproductive problem	8	5	0	0
Vascular event	1	1	0	0	0	1	0	0
Total adverse events	718	959	99	135
Total serious adverse events					18	23	5	1
Definitely not related to study drug					1	11	2	1
Probably not related to study drug					8	7	0	0
Possibly related to study drug					5	3	3	0
Probably related to study drug					4	2	0	0

^*Adverse events were assessed with the use of the Common Terminology Criteria for Adverse Events (version 3.0). Details of the statistical analysis plan for adverse events are provided in the Supplementary Appendix.

^†A level 5 serious adverse event due to intracranial hemorrhage resulted in the death of one patient in the 18th month after the beginning of the study (the 6th month of the observation period).