A Special Terpene Combination (Rowatinex®) Improves Stone Clearance after Extracorporeal Shockwave Lithotripsy in Urolithiasis Patients: Results of a Placebo-Controlled Randomised Controlled Trial

Abstract

Objective: To investigate the safety and efficacy of a special terpene combination in the treatment of patients with urolithiasis after extracorporeal shockwave lithotripsy (ESWL). Patients and Methods: 222 patients with clinically stable kidney or ureter stones of 0.3–2.0 cm undergoing complication-free ESWL were randomised to receive a special terpene combination (Rowatinex®; 3 × 2 capsules/day) or placebo. The study consisted of a 12-week active treatment phase and a 2-week follow-up phase. All patients had a physical examination, and diagnosis of kidney stones was made by X-ray, intravenous pyelogram or ultrasound at weeks 1, 4, 8 and 12 as well as after 2 weeks of follow-up. Stone-free status was defined as obviously successful expulsion of calculi/fragments, being without any stone. Results: In all, when compared to placebo, significantly more patients receiving the terpene combination treatment in the intent-to-treat (ITT) group [72 (67.9%) vs. 49 (50.0%); p = 0.0009] and the per-protocol (PP) group [69 (78.4%) vs. 48 (52.2%); p = 0.0004] were stone-free at the end of the study. Treatment with the terpene combination was also more effective when analysed with respect to the size of the treated stone. In addition, treatment with the terpene combination significantly reduced the median time to stone-free status from 85.0 to 56.0 days (p = 0.0061) and from 85.0 to 49.5 days (p = 0.0028) in the ITT and PP populations, respectively. Nine mild-to-moderate adverse events (AE; terpene combination group: 7 AE in 4 patients; placebo group: 2 AE in 2 patients) were assessed as drug-related. Conclusions: Treatment with the terpene combination is well tolerated and safe. The terpene combination was found to be an efficacious treatment in eliminating calculi fragments generated by ESWL as compared to placebo. The pharmacodynamic properties of the terpene combination (antilithogenic, antibacterial, antiinflammatory, spasmolytic and analgesic effects), which have been also confirmed in preclinical studies, represent a valuable alternative to the different drugs used in the treatment of urolithiasis.

The Effect of Terpene Combination on Ureter Calculus Expulsion After Extracorporeal Shock Wave Lithotripsy

“…Previous studies have reported that Rowatinex can help with the removal of remnant stone after SWL [10]. Rowatinex is an essential oil of terpenic type that consists of pinene (3%), camphene (15%), borneol (10%), anethol (4%), and cineol (3%).…”

“…Inhibition of remnant stone formation originating after SWL might increase the long-term success rate of SWL [16]. In addition, Rowatinex has shown antibacterial effects against a variety of pathogens [10]. Rowatinex has anti-inflammatory and analgesic properties derived from cineole and anethole, which are important to patients who have urolithiasis with spasm, inflammation, pain, and infection [17,18].…”

“…However, the number of subjects in that study was small, and the authors did not consider stone size and treatment duration. In a randomized trial conducted by Romics et al [10], the expulsion rate of urinary stones was greater and the treatment duration was shorter in the Rowatiex group than in the placebo group; no significant differences in age, sex, or stone size were found between the two groups. The expulsion rate of urinary stones 2 weeks after the initial SWL was not significantly different between the two groups (37.4% compared with 35.5%, p=0.684).…”

In vitro Dissolution of Calcium Oxalate Stones with Ethylenediaminetetraacetic Acid and Snake Venom Thrombin-Like Enzyme

“…When surgery or pharmacologic therapies fail, appropriate chemical treatments may provide a useful adjunct for improving the efficacy of stone comminution during therapy [9] and are typically delivered via a nephrostomy tube. Currently, hemiacidrin and tromethamine have been shown to be efficacious agents both in vitro and in clinical trials [10,11], and the terpene combination facilitated the elimination of stone fragments [12]; however, the dissolution of calcium oxalate stones is complicated by the fact that most of them are hard and large and with non-uniform formations.…”

Untitled

“…[7] Another study designed to investigate the safety and efficacy of a special terpene combination in the treatment of patients with urolithiasis after extracorporeal SWL (ESWL) revealed that it was a well-tolerated, safe, and efficacious therapy for eliminating calculi fragments generated by ESWL when compared to a placebo treatment. [8] Undoubtedly, it is crucial to optimize health care for nephrolithiasis by choosing an ideal treatment that is economical for patients, but still safe and effective. Therefore, the objective of this study was to compare the treatment costs and treatment durations between Rowatinex ® and DSE in patients suffering from nephrolithiasis in Vietnam.…”