Table 3.
Adverse Events during the Clinical Trial Intervention Period (through August 20, 2015).
| Event* | Intensive Treatment (N = 4678) | Standard Treatment (N =4683) | Hazard Ratio (95% Cl) | P Value† | ||
|---|---|---|---|---|---|---|
| no. of participants | % per year | no. of participants | % per year | |||
| Serious adverse event‡ | 1799 (38.5) | 14.8 | 1742 (37.2) | 14.2 | 1.04 (0.97–1.11) | 0.23 |
| Conditions of interest | ||||||
| Serious adverse event | ||||||
| Hypotension | 99 (2.1) | 0.7 | 58 (1.2) | 0.4 | 1.71 (1.24–2.38) | 0.001 |
| Syncope | 97 (2.1) | 0.6 | 73 (1.6) | 0.5 | 1.33 (0.98–1.81) | 0.07 |
| Bradycardia | 78 (1.7) | 0.5 | 68 (1.5) | 0.5 | 1.15 (0.83–1.59) | 0.41 |
| Electrolyte abnormality | 138 (2.9) | 0.9 | 104 (2.2) | 0.7 | 1.33 (1.03–1.72) | 0.03 |
| Injurious fall§ | 102 (2.2) | 0.7 | 101 (2.2) | 0.7 | 1.01 (0.76–1.33) | 0.97 |
| Acute kidney injury or acute renal failure¶ | 193 (4.1) | 1.3 | 115 (2.5) | 0.8 | 1.69 (1.34–2.13) | <0.001 |
| Emergency department visit or serious adverse event | ||||||
| Hypotension | 144 (3.1) | 1.0 | 79 (1.7) | 0.5 | 1.83 (1.40–2.42) | <0.001 |
| Syncope | 148 (3.2) | 1.0 | 100 (2.1) | 0.7 | 1.48 (1.15–1.92) | 0.002 |
| Bradycardia | 94 (2.0) | 0.6 | 76 (1.6) | 0.5 | 1.24 (0.91–1.68) | 0.17 |
| Electrolyte abnormality | 170 (3.6) | 1.1 | 127 (2.7) | 0.9 | 1.34 (1.07–1.69) | 0.01 |
| Injurious fall§ | 335 (7.2) | 2.3 | 317(6.8) | 2.2 | 1.06 (0.91–1.23) | 0.49 |
| Acute kidney injury or acute renal failure¶ | 201 (4.3) | 1.3 | 120 (2.6) | 0.8 | 1.69 (1.35–2.12) | <0.001 |
| Monitored clinical events: adverse laboratory measures║ | ||||||
| Serum sodium <130 mmol/liter | 189 (4.0) | 1.3 | 103 (2.2) | 0.7 | 1.85 (1.46–2.36) | <0.001 |
| Serum sodium >150 mmol/liter | 6 (0.1) | 0.04 | 0 | 0 | — | 0.004 |
| Serum potassium <3.0 mmol/liter | 117 (2.5) | 0.8 | 75 (1.6) | 0.5 | 1.56 (1.17–2.10) | 0.002 |
| Serum potassium >5.5 mmol/liter | 184 (3.9) | 1.2 | 173 (3.7) | 1.2 | 1.06 (0.86–1.31) | 0.56 |
Duplicate events of the same (i.e.,in the same row) in a given participant were counted only once, but the same participant could be included in more than one row for the same event.
Inferences drawn from these tests may not be reproducible, since none of the P values or 95% confidence intervals were adjusted for multiplicity.
A serious adverse event was defined as an event that was fatal or life-threatening, that resulted in significant or persistent disability, that led to or prolonged a hospitalization, or that was an important medical event that the investigator judged to be a substantial hazard or harm to the participant that may have led to medical or surgical intervention to prevent one of the other events listed above.
Injurious fall was defined as a fall that resulted in evaluation in an emergency department or that resulted in hospitalization.
Acute kidney injury or acute renal failure was coded if the diagnosis was listed in the hospital discharge summary and was thought to be one of the top three reasons for admission or continued hospitalization. Although acute kidney injury was not reportable as a condition of interest if it resulted only in evaluation in an emergency department, it was noted in a few cases (8 in the intensive-treatment group and 5 in the standard-treatment group) in which the participant presented to an emergency department for one of the other conditions of interest.
Adverse laboratory measures were detected on routine or unscheduled tests; routine laboratory tests were performed at 1 month, then quarterly during the first year, then every 6 months.