WMU-NPC-1

16 evidence topics · 1 source

Objective

Efficacy, safety, and concentration selection

“It aimed to evaluate the efficacy and safety of topical sirolimus gel (NPC-12G) and to estimate the optimal concentration for treatment of cutaneous lesions of VAs.” (opens the source at this quote in a new tab)
“The efficacy, safety, and optimal concentration of topical sirolimus gel for treatment of cutaneous lesions of vascular anomalies requires evaluation.” (opens the source at this quote in a new tab)

Location and study date

No evidence found.

Study design

Multicenter randomized parallel-group study

“double-blind, placebo-controlled, parallel-group” (opens the source at this quote in a new tab)

Eligibility criteria

Age and lesion requirements for entry

“Patients who are at least 1 month old” (opens the source at this quote in a new tab)
“patients with target lesions that did not show a tendency to regress within 4 weeks based on interviews and which were visible in photographs” (opens the source at this quote in a new tab)

Exclusions for prior mTOR inhibitor and local treatment

“Patients who had received oral treatment with mTOR inhibitors (sirolimus, everolimus, temsirolimus, etc.) within the 12 weeks prior to registration.” (opens the source at this quote in a new tab)
“Patients who had received treatment for the target lesion (surgical treatment, endovascular treatment, laser therapy, phototherapy, liquid nitrogen therapy, or elastic bandage) within 3 months prior to registration.” (opens the source at this quote in a new tab)
“Patients with severe erosions or ulcers on the target lesion.” (opens the source at this quote in a new tab)

Treatment

Alternative sirolimus gel concentrations and treatment schedule

Field	Quoted value
Lower active concentration	“0.2%”
Higher active concentration	“0.4%”
Schedule	“twice per day for 12 weeks.”

Study outcomes

Rationale for using photographic overall improvement score as the primary endpoint

Independent photographic assessment at week 12

“overall improvement score” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Enrolled participants by diagnosis

Diagnosis	Quoted count
Venous malformation	“27”
Lymphatic malformation	“14”
Tufted angioma	“8”
Kaposiform hemangioendothelioma	“1”

Description of analysis sets

Safety, full analysis, and per protocol sets

“all 50 enrolled subjects were included in the safety analysis set” (opens the source at this quote in a new tab)
“There were also no case excluded from the full analysis set as there were no violations of eligibility criteria that could have affected efficacy, making the same population as the safety analysis set.” (opens the source at this quote in a new tab)
“one case in the 0.2% group and two cases in the 0.4% group were excluded from the per protocol set due to low compliance.” (opens the source at this quote in a new tab)

Results

Participant disposition

Screening, randomization, and dropouts

“Fifty patients were screened for eligibility, all of whom underwent randomization. After the trial started, three patients dropped out due to low compliance.” (opens the source at this quote in a new tab)

Baseline characteristics

No evidence found.

Efficacy results

Primary endpoint: comparisons with placebo

Active concentration	Quoted p-value
0.2% gel	“0.410”
0.4% gel	“0.549”

Primary endpoint: investigator conclusion

“There was no statistically significant difference in the mean improvement score in the 0.2% group (p = 0.410) or the 0.4% group (p = 0.549) compared with in the placebo group.” (opens the source at this quote in a new tab)
“Thus, we could not prove the efficacy of topical sirolimus for cutaneous vascular anomalies in this protocol.” (opens the source at this quote in a new tab)

Secondary and post hoc lesion-size findings

“the improvement in target lesion size at Week 12 assessed by the committee as one of the 16 secondary endpoints was significantly higher in the 0.4% sirolimus gel group than in the placebo group (p = 0.031).” (opens the source at this quote in a new tab)
“In the post-hoc analysis outside the protocol tracing the contour of the lesion, the percentages of patients with ≥20% reduction in the lesion area increased dose-dependently (0%, 37.5%, and 65.0% in the placebo, 0.2%, and 0.4% group, respectively).” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Application-site adverse events in the 0.4% group

“irritation and dermatitis” (opens the source at this quote in a new tab)

Overall safety assessment

“Regarding safety, irritation and dermatitis at the application site occurred in the 0.4% gel group.” (opens the source at this quote in a new tab)
“The safety data demonstrated topical sirolimus to have an acceptable safety profile.” (opens the source at this quote in a new tab)

Study limitations

Summary

This randomized study evaluated 0.2% and 0.4% topical sirolimus gels, not QTORIN rapamycin 3.9% gel. The diagnostic counts total 50 participants, including 14 with lymphatic malformations. Neither active concentration differed significantly from placebo on the primary photographic improvement endpoint. A lesion-size finding was one of 16 secondary endpoints, and the lesion-area responder analysis was post hoc. The heterogeneous population and different formulations limit application of these results to QTORIN or specifically to microcystic lymphatic malformations.

Investigator-stated limitation and call for confirmatory evidence

“As a primary endpoint, this trial failed to demonstrate the efficacy of sirolimus gel for VA skin lesions. However, secondary endpoint and post-hoc analyses showed the possibility that sirolimus gel reduced the size of lesions.” (opens the source at this quote in a new tab)
“To confirm these findings, a precise, long-term, randomized clinical trial with a larger patient group that focuses on lesion size as an endpoint is necessary.” (opens the source at this quote in a new tab)