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Abstract: TH-PO324

Efficacy of Low-Dosage Tolvaptan for Treatment of Profound Hyponatremia in Syndrome of Inappropriate Antidiuresis: An Open-Label Randomized Controlled Trial

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Krisanapan, Pajaree, Thammasat University Hospital, Khlong Nueng, Pathum Thani, Thailand
  • Chinpraditsuk, Sutatip, Thammasat University Hospital, Khlong Nueng, Pathum Thani, Thailand
  • Jaiyen, Narongchai, Thammasat University Hospital, Khlong Nueng, Pathum Thani, Thailand
  • Tantiyavarong, Pichaya, Thammasat University Hospital, Khlong Nueng, Pathum Thani, Thailand
  • Pattharanitima, Pattharawin, Thammasat University Hospital, Khlong Nueng, Pathum Thani, Thailand
Background

It is commonly accepted that the first-line treatment of syndrome of inappropriate antidiuresis (SIAD) is fluid restriction (FR). However, the second-line treatments are still controversial among guidelines. This study investigates whether tolvaptan is more effective than FR combined with furosemide (FSM) and sodium chloride (NaCl) tablets in treating SIAD patients who likely to fail from FR alone.

Methods

We conducted a 28-day single-center, open-label, randomized controlled trial in patients with profound hyponatremia (serum sodium concentration, [Na+] ≤ 125 mmol/L) who showed signs of FR failure in SIAD. Patients were randomly assigned to either the tolvaptan group (received tolvaptan 7.5 mg/day) or the control group (received FR of 800 ml/day, FSM 20–40 mg/day, and NaCl 3 g/day). The primary endpoint measured the change in [Na+] from baseline to day 4. The protocol was registered on thaiclinicaltrial.gov (TCTR20210628004).

Results

In the analysis of 29 patients (13 on tolvaptan and 16 on control), baseline [Na+] averaged was 120 ± 3 mmol/L in both groups. Tolvaptan significantly increased the change in mean [Na+] on day 4 compared to the control with 12.2±3.4 and 6.3±6.0 mmol/L (p=0.004), respectively. Notable differences persisted days 7 and 14 but not at day 28 (Figure 1A). The actual [Na+] was shown on Figure 1B. At days 4, the proportion of patients with [Na+] ≥ 130 mmol/L was achieved by 76.9% on tolvaptan and 25% on control (p = 0.009). Median time [IQR] to restore [Na+] ≥ 130 mmol/L was 2 [1, 14] days with tolvaptan and 14 [3, 14] days with control (p=0.059). In terms of safety, tolvaptan showed fewer cases of hypokalemia (p=0.044) than the control. However, 3 tolvaptan patients developed sodium overcorrection without statistical significance (p=0.078).

Conclusion

In profound SIAD with clinical features suggesting failure with fluid restriction alone, tolvaptan significantly increases [Na+] without causing significant sodium overcorrection.

Figure 1A and 1B