The comparative efficacy research to assess the use of RFA and VATS for PHH was an investigator-initiated, controlled cohort study done at 14 centers in China between 2015 and 2019.
Eligible participants were aged 14 years or older, were diagnosed as primary PHH who are undergone treatment options with RFA or VATS. Exclusions included patients who are non-palmar hyperhidrosis, and non-interventional treatment for hyperhidrosis. The study was approved by institutional ethics committees at the principal investigator center in September 16, 2020, and it was being recognized in other 13 centers. This study was registered with the China Clinical Trials Registry in November 1, 2020 (ChiCTR2000039576). All patient’s provided written informed consent before RFA or VATS for treatment PHH. The study was done per the Declaration of Helsinki and Good Clinical Practice principles.
The treatment options were done according to a prespecified analysis plan within between RFA and VATS framework. Per a prospective exposure factor definition, patients excluded who were secondary hyperhidrosis before RFA or VATS.
Patients of this study cohort included two distinct groups: The RFA group, which comprised patients who underwent RFA applied unilaterally, and the control (VATS) group, which the VATS were performed sympathectomy (Thoracic 4 and or Thoracic 3 ganglia according to actual condition) by video-assisted thoracoscopic, under general anesthesia with double-lumen endotracheal intubation.[16, 18, 29] In the RFA group, the operation technique of RFA for PHH according to local practice at the study centers because there are no authoritative practical guidelines. Rejoice, in fact, we find that the patients underwent a homogeneity technique protocol at participate centers, which following subcutaneous local anesthetic infiltration, a 5 mm active cannula of the RFA device was advanced to the thoracic 4 sympathetic ganglions under fluoroscopic guidance (X-ray Computed Tomography). When the probe reached the desired point, the level of the cannula was tested by 3-Dimension’s image reconstruction. After neurophysiological testing, RFA thermal coagulation was applied at 90 degree C for 180 seconds, and 2 ml of 2% lidocaine was spread through the cannula after thermal coagulation in necessary. The decision to treatment options for PHH was not determined by study design, but instead was based on the decision of the physician and the patient, and may be influenced by regional health policy practices (Social Security fund policy and Medical Insurance Policy).
Control variables included the demographic data, clinical disease (Hyperhidrosis Disease Severity Scale [HDSS]), quality of life (QOL) questionnaire, and family history were collected at preoperative from the medical charts each of participation center. The HDSS questionnaire are consists of four statements, each receiving a score of 1 to 4, with 1 being the mildest grade and 4 the worst. The QOL questionnaire is consists of twenty statements, each receiving a score of 1 to 5, with 20 being the mildest grade and 100 the worst. Outcomes variable included the clinical efficacy, safety (intraoperative and postoperative complication),[31, 32] patient satisfaction, HDSS and QOL questionnaire, compensatory hyperhidrosis, and symptom recurrence follow-up data of postoperative months 1, 3, 6, and 12 (1 year), as previously reported.[16, 33] For patient satisfaction is used the chief complaint of patients by phone call and return follow-up to respectively evaluated. To evaluate the postoperative QOL is used the last data of follow-up questionnaire. All follow-up was implemented by an external blinded endpoint committee (setting at the principal investigator institution).
The primary outcome was the clinical efficacy in 1-year. The success of clinical efficacy was defined as complete remission after treatment for PHH, and the ineffective treatment was defined as no remission or a few partial remissions after treatment for PHH. Surgical failure was defined as nothing improvement for hyperhidrosis symptoms in postoperative. The HDSS and QOL were assessed respectively in preoperative and postoperative as a component of the primary outcome were determined. The secondary outcomes were including symptom recurrence, complication, compensatory hyperhidrosis, patient satisfaction, length of stay, and hospital costs.
Sample size calculation
The study sample included patients aged ≥14 year who received RFA or VATS for PPH. Assuming an efficacy rate of 68%-100% with VATS by a report of published literature. Per a power analysis of equivalence tests of two independent proportions using PASS 11 software (NCSS, LLC. Kaysville, Utah, USA.). Sample sizes of 150 in the treatment group and 150 in the control group achieve 90% power to detect equivalence. The margin of equivalence, given in terms of the difference, extends from 0.20 to 0.20. The calculations assume that two, one-sided Z tests are used. The significance level is Alpha targeted at 0.05.
The RFA and VATS cohorts were analyzed separately for HDSS and QOL in preoperative and postoperative. The patients with the loss to follow-up will be excluded from the study analysis. In patients with PHH, baseline characteristics were compared between patients receiving RFA and VATS using standardized mean differences (SMD). The propensity score for receiving RFA was estimated using a logistic regression model. Covariates included in the model were demographics (age and sex), family history, HDSS and QOL in preoperative. Propensity-score matching was implemented using a nearest-neighbor strategy, with a minimum caliper of 0.1.[34, 35] The ratio was one patient receiving RFA matched with one patient receiving VATS. The SMD was used to assess the balance of baseline covariates between the RFA and VATS groups in the matched cohort. An SMD of less than 0.10 indicated a good balance. In the matched cohort, the non-normally distributed of the length of stay and hospitalization costs were converted to categorical variables based on the median. The primary outcome and secondary outcomes for compared the distributions of categorical variables using the chi-square test in the unmatched cohort and a logistic-regression models in the matched cohort, which is reported with odds ratios (OR) and 95% confidence intervals (CI) for two treatment group. To test whether the findings of the patient-level analysis might be due to a causal effect of RFA, we used a further adjusted time-varying Cox proportional hazard model to estimate the hazard ratio for ineffective treatment in the matched cohort.
Statistical analyses were carried out using R 3.6.3 software.