Combining idrevloride and hypertonic saline in treatment of primary ciliary dyskinesia improves lung function and QOL without risk for hyperkalemia.

The treatment of primary ciliary dyskinesia (PCD) patients with a combination of idrevloride and hypertonic saline (HS) resulted in significant improvement of percent predicted (pp) FEV₁ compared with saline alone or placebo after 1 month. The treatment did not lead to evidence of hyperkalemia

The phase 2 CLEAN-PCD trial investigated the sodium channel blocker idrevloride for its safety and efficacy in therapy of PCD. When combined with hypertonic saline, two actions were predicted: the saline on one hand draws water into the airway lumen and idrevloride on the other hand stimulates the secretion of chloride while inhibiting sodium and water absorption, thus rehydrating the mucus in the airway lumen.

The multinational trial included 123 patients of at least 12 years of age who were randomly assigned to four different regimens over 28 days in part A of the study: HS or idrevloride alone, combination of HS with idrevloride, or placebo. Then, treatments were crossed over for another 28 days, after a washout period of 4 weeks. “Individuals were also invited to continue their current therapy for another 28 days in part B, where we added ivacaftor a CFTR [cystic fibrosis transmembrane conductance regulator]–modifying drug to see if that improved mucus hydration even further,” said Thomas Ferkol, MD, who presented these findings at the 2023 ERS International Congress.

All members of the study cohort were on stable therapy. Baseline observations found a mean age of 28 years, a mean ppFEV₁ of 66 and a mean ppFVC of 84. “We were able to demonstrate that the individuals who were receiving combination therapy, had a greater effect than individuals, who were just receiving hypertonic saline which was our primary comparator in this study,” Dr. Ferkol said. Also, the absolute change from baseline in ppFEV₁ was statistically significantly greater on HS plus idrevloride versus HS alone (+1.0 vs -0.5; P=0.04). Similarly, ppFVC ameliorated most on the combination treatment: +1.3 vs −0.1 in contrast to HS alone (P=0.03) and +1.3 vs −2.1 in the comparison to placebo (P=0.01), respectively. Adding ivacaftor to the medication regimen in part B of the trial, however, did not affect pulmonary function. “But what we did find is that in individuals who were treated for 2 months as opposed to 1 month with the drug, there appeared to be a greater absolute change in ppFEV₁,” Dr. Ferkol added.

Moreover, parameters of QOL were improved. Adverse events were consistent with PCD manifestations, and no evidence of hyperkalemia was found. Based on these results, idrevloride for PCD is currently advanced to phase 3 investigations.

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