Table 2.
Safety and tolerability outcomesa
| Outcome | Intention-to-treat |
On-treatment |
||
|---|---|---|---|---|
| Dose titration (N = 39) | Follow-up (N = 36) | Dose titration (N = 38) | Follow-up (N = 31) | |
| Safety | ||||
| Serum potassium <3.2 mEq/l | 0 | 0 | 0 | 0 |
| Serum magnesium <0.8 mg/dl | 0b | 0 | 0b | 0 |
| Serum corrected calcium <7.0 mg/dl | 0 | 0 | 0 | 0 |
| Serum furosemide level >12 mcg/l | 0 | 0 | 0 | 0 |
| Dialysis-associated hypotension | 0 | 0 | 0 | 0 |
| Severe or very severe rash | 0 | 0 | 0 | 0 |
| Severe or very severe hearing change | 0 | 0 | 0 | 0 |
| Severe or very severe tinnitus | ||||
| Events per 100 person-wks | 1 | 2 | 1 | 1 |
| Proportion of participants with ≥1 event | 1 (3%)c | 1 (3%)c | 1 (3%)c | 1 (3%)c |
| ≥10-point decline in inner EAR score | ||||
| Events per 100 person-wks | 0.9 | 3 | 1 | 4 |
| Proportion of participants with ≥1 event | 1 (3%) | 3 (8%) | 1 (3%) | 3 (10%) |
| Tolerability | ||||
| Severe or very severe cramping | ||||
| Events per 100 person-wks | 12 | 11 | 11 | 10 |
| Proportion of participants with ≥1 event | 10 (26%) | 9 (25%) | 10 (26%) | 9 (29%) |
| Severe or very severe dizziness/presyncope | ||||
| Events per 100 person-wks | 3 | 0.5 | 2 | 0.6 |
| Proportion of participants with ≥1 event | 5 (13%) | 1 (3%) | 5 (13%) | 1 (3%) |
| Severe or very severe unusual tiredness | ||||
| Events per 100 person-wks | 0 | 1 | 0 | 1 |
| Proportion of participants with ≥1 event | 0 (0%) | 2 (6%) | 0 (0 %) | 2 (6%) |
| Severe or very severe nausea | ||||
| Events per 100 person-wks | 3 | 2 | 3 | 2 |
| Proportion of participants with ≥1 event | 5 (13%) | 3 (8%) | 5 (13 %) | 3 (10%) |
| Severe or very severe vomiting | ||||
| Events per 100 person-wks | 0.4 | 2 | 0.5 | 1 |
| Proportion of participants with ≥1 event | 1 (3%) | 2 (6%) | 1 (3%) | 2 (6%) |
| Severe or very severe diarrhea | ||||
| Events per 100 person-wks | 0.4 | 2 | 0.5 | 3 |
| Proportion of participants with ≥1 event | 1 (3%) | 4 (13%) | 1 (3%) | 4 (13%) |
EAR, effectiveness of auditory rehabilitation.
Serum laboratory values were assessed every week during dose titration and every 4 weeks during follow-up. Dialysis-associated hypotension was assessed during each treatment throughout the study. Symptoms were assessed every week during dose titration and every 2 weeks during follow-up, each with a 1-week recall period. Hearing was assessed every 2 weeks during dose titration and every 4 weeks during follow-up, each with a 1-week recall period.
One participant was missing serum magnesium values at weeks 3 and 4 (laboratory error).
One participant reported severe tinnitus a total of 9 times during the study, stating that it was a long-standing symptom that was unchanged during the study period. The participant discontinued study furosemide in week 9 because of perceived inefficacy of study medication and concern about falls, and continued to report severe tinnitus after discontinuation of study furosemide.