Table 5.
Conivaptan studies in patients with hyponatremia
| Baseline Na+ | Ghali et al59 | Annane et al60 | Zeltser et al61 | Verbalis et al62 | Ghali et al73 | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total number of patients | 74 | 83 | 84 | 251 | HF 98 | No HF 237 | |||||||||||||
| Ethnicity | 89% Whites | 100% Whites | 85.7% Whites | _ | Placebo | 20 mg | 40 mg | 80 mg | Placebo | 20 mg | 40 mg | 80 mg (Whites) | |||||||
| Females | 51.4% | 33.7% | 51.2% | _ | 78 | 90 | 83 | 63 | 95 | 85 | 92 | 78 | |||||||
| Age > 65 | 68% | 47% | 71.4% | _ | 44 | 60 | 54 | 38 | 50 | 67 | 70 | 50 | |||||||
| Age | _ | _ | _ | _ | 89 | 80 | 79 | 63 | 90 | 89 | 74 | 78 | |||||||
| Euvolemic % | 75% | 62.7% | 66.7% | _ | 75.7 | 69 | 73.1 | 70.8 | 75.7 | 75.1 | 71.7 | 73.7 | |||||||
| Design | Double-blinded, placebo-controlled | Double-blinded, placebo-controlled | Double-blinded, placebo-controlled | Open label | Double-blind placebo-controlled (n = 184) open label (n = 251) | ||||||||||||||
| iv or oral conivaptan | Oral | Oral | iv | iv | iv | ||||||||||||||
| Dose of conivaptan | Placebo or conivaptan 40 or 80 mg/d in 2 divided doses | Placebo or conivaptan 40 or 80 mg/d in 2 divided doses | Placebo or 20 mg of conivaptan as a bolus iv dose, followed by a continuous infusion of 40 or 80 mg/d | Loading dose of iv conivaptan 20 mg followed by a continuous iv infusion of conivaptan 20 or 40 mg/d | Loading dose of 20 mg followed by continous infusion 40 or 80 mg/d | ||||||||||||||
| Duration of treatment | 5 days | 5 days | 4 days | 4 days | 4 days | 4 days | |||||||||||||
| Primary endpoint | Placebo | 40 mg/d (P) | 80 mg/d (P) | Placebo | 40 mg/d (P) | 80 mg/d (P) | Placebo | 40 mg/d (P) | 80 mg/d (P) | 20 mg/d | 80 mg/d | Placebo | 20 mg/d | 40 mg/d | 80 mg/d | Placebo | 20 mg/d | 40 mg/d | 80 mg/d |
| LS mean change from baseline in serum [Na+] AUC during the 5-day treatment ± SE (mEq h/L) |
309.2 | 621.3 (0.03) | 836.2 (<0.001) | 88 ± 81 | 634 ± 84 (0.0001) | 953 ± 86 (0.0001) | 12.9 | 490.9 (<0.001) | 716.6 (<0.001) | 753.8 | 689.2 | 93 | 459.0 | 579.0 | 576.0 | 47.0 | 867.0 | 703.0 | 700.0 |
| Secondary endpoints | Placebo | 40 mg/d (P) | 80 mg/d (P) | Placebo | 40 mg/d (P) | 80 mg/d (P) | Placebo | 40 mg/d (P) | 80 mg/d (P) | 20 mg/d | 80 mg/d | Placebo | 20 mg/d | 40 mg/d | 80 mg/d | Placebo | 20 mg/d | 40 mg/d | 80 mg/d |
| Time to a confirmed increase in serum [Na+] ≥ 4 mEq/L from baseline (median h) | 71.7 | 27.5 (0.044) | 12.1 (0.002) | _ | 23.5 (0.0004) | 8.7 (0.0001) | _ | 23.7 (<0.001) | 23.4 (<0.001) | _ | _ | NE | 30.0 | 28.0 | 24.0 | NE | 18.0 | 24.0 | 8.0 |
| Total time serum [Na+] ≥ 4 mEq/L above baseline [LS mean (SE)•h] | 46.5 | 69.8 (0.103) | 88.8 (0.001) | 20.3 | 68.8 (0.0001) | 86.6 (0.0001) | 14.2 | 53.2 (<0.001) | 72.7 (<0.001) | _ | _ | ||||||||
| Change in serum [Na+] to end of treatment [LS mean (SE) mEq/L] | 3.4 | 6.4 (0.081) | 8.2 (0.002) | 1.6 | 7.2 (0.0001) | 9.1 (0.0001) | 0.8 | 6.3 (<0.001) | 9.4 (<0.001) | _ | _ | 3.0 | 7.9 | 7.9 | 9.0 | 3.1 | 9.8 | 8.1 | 9.4 |
| Patients with a confirmed normal serum [Na+] (≥ 135 mEq/L) or increase of ≥6 mEq/L [no. (%)] | 11 | 17 (0.111) | 22 (0.014) | 20 | 66.7 (0.0008) | 88.5 (<0.0001) | 20.7 | 69 (<0.001) | 23 (<0.001) | _ | _ | 11 | 50 | 63 | 88 | 25 | 78 | 75 | 89 |
Abbreviations: AUC, area under the curve; iv, intravenous; HF, heart failure; NE, not estimable.