Analgesic Efficacy of Mirogabalin in Patients With Herpes Zoster: Protocol for a Prospective Multicenter Randomized...

Herpes zoster (HZ) is a debilitating condition characterized by acute dermatomal pain and a high risk of developing postherpetic neuralgia (PHN). Although early antiviral therapy is essential, its analgesic efficacy is often insufficient, particularly in patients with moderate to severe pain. While gabapentinoids are recommended as adjunctive analgesics, current options like gabapentin and pregabalin are often limited by inconsistent efficacy and dose-dependent adverse events. Mirogabalin, a novel gabapentinoid with higher affinity and selective dissociation for the a2d subunit, may offer superior pain relief with a wider safety margin. However, although mirogabalin has demonstrated efficacy in PHN, its analgesic efficacy and safety in patients with acute HZ-associated pain have not been adequately established.

To test the hypothesis that conventional treatment combined with mirogabalin provides superior pain relief compared to conventional treatment alone in patients with HZ.

Multicenter, prospective, randomized, open-label, blinded-endpoint trial.

Beijing Tiantan Hospital, Second Hospital of Hebei Medical University, and Second Hospital of Shanxi Medical University.

A total of 750 adult patients experiencing moderate to severe pain with rash onset within the last 30 days will be enrolled. Patients will be randomly assigned in a 1:1 ratio to either mirogabalin group or control group. The mirogabalin group will receive oral mirogabalin in addition to conventional treatment, while the control group will receive conventional treatment alone. Mirogabalin will be titrated from 5 mg twice daily to a maximum of 15 mg twice daily according to individual tolerability and will be used during the prespecified treatment period up to 90 days after rash onset. After 90 days following rash onset, treatment will be identical in both groups, and patients with persistent pain meeting the definition of PHN will receive standardized guideline-based PHN management. The study duration will be 52 weeks. Patients and treating physicians will be aware of treatment allocation, whereas outcome assessors will remain blinded.

The primary outcome is the average pain intensity at week 4. Secondary outcomes include the worst pain intensity, proportions of patients achieving ≥ 30% and ≥ 50% pain reduction, proportion of patients developing postherpetic neuralgia, type of analgesics and average weekly consumption per analgesics, the Herpes Zoster Severity of Illness Index, quality of life assessed by the 12-item Short Form Health Survey, sleep quality assessed by the Medical Outcomes Study Sleep Scale, the Neuropathic Pain Scale, and adverse events. These outcomes will be assessed at prespecified time points from baseline through week 52, according to the assessment schedule for each outcome. Statistical analyses will be performed based on the modified intention-to-treat population.

The open-label design may introduce performance bias, although blinded endpoint assessment is intended to minimize this effect. Second, the findings may not be generalizable to patients with subacute HZ, PHN, or advanced chronic kidney disease.

If mirogabalin combined with conventional treatment proves more effective and better tolerated than conventional treatment alone, it could establish a new evidence-based standard for optimizing pain management in patients with HZ.