Efficacy and safety of Diclofenac sodium plaster in patients with acute pain of the limbs: a randomized, placebo and active-controlled, double-blind, parallel-group trial.

OBJECTIVE: The aim of the present study was to assess the safety and efficacy of Diclofenac sodium (DS) 140 mg medicated plaster vs. Diclofenac epolamine (DIEP) 180 mg medicated plaster and placebo plaster, for the treatment of painful disease due to traumatic events of the limbs. PATIENTS AND METHODS: This was a multicenter, phase III study involving 214 patients, aged 18-65 years, affected by painful conditions due to soft tissue injuries. Patients were randomized to DS, DIEP or placebo arms and treated with once-daily application of the plaster for a total treatment period of 7 days. The primary objective was first to demonstrate the non-inferior efficacy of the DS treatment when compared to the reference DIEP treatment and second that both, test and reference treatments, were superior with respect to placebo. The secondary objectives included the evaluation of efficacy, adhesion, safety, and local tolerability of DS in comparison to both DIEP and placebo. RESULTS: The mean visual analog scale (VAS) score decrease for pain at rest was higher in the DS (-17.65 mm) and the DIEP group (-17.5 mm) than in the placebo (-11.3 mm). Both active formulation plasters were associated with a statistically significant pain reduction compared to placebo. No statistically significant differences were observed between DIEP and DS plasters efficacy in relieving pain. Secondary endpoint evaluations supported the primary efficacy results. No serious adverse events (SAEs) were registered, and the most commonly detected adverse events were skin reactions at the application site. CONCLUSIONS: The results showed that both the DS 140 mg plaster and the reference DIEP 180 mg plaster are effective in relieving pain and present a good safety profile.

Effectiveness of hyaluronate-based pessaries in the treatment of vulvovaginal atrophy in postmenopausal women.

Objectives: This study aimed to assess the efficacy and safety of hyaluronic acid-based vaginal pessaries (Hydeal-D) in the treatment of vulvovaginal atrophy (VVA).Study design: The study was a prospective, multicenter clinical investigation of VVA topical treatment in 40 postmenopausal women. Patients applied one Hydeal-D pessary every 3 days for 3 months.Main outcome measures: The primary endpoint was the amelioration of VVA signs after treatment, evaluated by measuring the change from baseline of the Vaginal Health Index (VHI) score. Secondary endpoints included the evaluation of other VVA-related signs and symptoms, safety, and patient-reported and clinician-reported satisfaction and treatment tolerability.Results: The 3-month treatment with Hydeal-D vaginal pessaries showed efficacy for all analyzed endpoints. Improvement exceeded threshold values of VVA diagnosis, sexual dysfunction, and distress, confirming clinically relevant amelioration of VVA symptoms. Changes from baseline conditions confirmed significant improvement of all parameters including the VHI, vaginal pH, patients' perception of VVA symptoms, sexual function, and vaginal maturation. Patients' overall satisfaction was very high after 1 month of treatment and increased further after 3 months. No severe adverse events were reported.Conclusions: Significant amelioration of VVA-related signs indicates that Hydeal-D vaginal pessaries are an effective, safe, and well-tolerated non-hormonal therapeutic option for VVA in postmenopausal women.

Efficacy and safety of a novel hydrogel (HYADD4-G) in degenerative disc disease patients: a multicentric open label study.

OBJECTIVE: In this premarket clinical study, we evaluated the efficacy and safety of a novel Hydrogel (HYADD4-G) for reducing low back pain (LBP) in patients with degenerative disc disease (DDD). PATIENTS AND METHODS: Twenty-three patients with chronic LBP were enrolled. All patients presented with up to three lumbar black discs (Pfirrmann grade III or IV), LBP of at least 40 mm on the Visual Analogue Scale (VAS), and a Roland-Morris Disability Questionnaire (RMDQ) score of at least 9. Patients received a single 1.5 ml intradiscal injection of HYADD4-G (8 mg/ml), guided by X-ray. Our primary endpoint was the change in VAS score from baseline (day 0) to 4, 12, and 24 weeks. Our secondary endpoints were black disc hydration by Magnetic Resonance Imaging (MRI); the patient's therapeutic response according to the RMDQ; the quality of life, as determined by the EuroQol-5 Dimension (EQ-5D) Index; and a global assessment of patient health status, safety, and local tolerability. RESULTS: Compared with baseline values, VAS score showed a significant reduction at each time point, and across the overall 24-week follow-up period (p < 0.0001). MRI scanning observed a significant reduction in Pfirrmann grade from baseline, by at least one grade, at both week 4 (p = 0.0039) and week 24 (p = 0.0010). Furthermore, compared with baseline values, there was a significant reduction in RMDQ score at each timepoint, and across the entire study period (p < 0.0001). The EQ-5D index increased significantly from baseline to week 24 (p = 0.0001). Finally, mean VAS scores for Patient Global Assessment (PTGA), and Clinical Observer Global Assessment (COGA), decreased significantly at each time point (p < 0.0001), except for week 4. CONCLUSIONS: HYADD4-G proved to be an efficient reliever of low back pain due to DDD.

Enzymatic debridement: is HA-collagenase the right synergy? Randomized double-blind controlled clinical trial in venous leg ulcers.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a new ointment containing Hyaluronic Acid and collagenase from non-pathogenic Vibrio alginolyticus. PATIENTS AND METHODS: Double blind, multicenter, controlled clinical trial (no. ISRCTN71239043) conducted to demonstrate the superiority of Hyaluronic Acid-Collagenase applied once a day over placebo in mean reduction of devitalized/fibrinous/slough tissue after 15 days of treatment. 113 patients with venous ulcers were enrolled and randomized to receive active treatment therapy or vehicle preparation. Both arms also received compression therapy. Subjects were assessed at baseline and at 4 different clinical study visits up to a maximum of 30 days. Outcome measures included mean percentage debridement evaluated by digital planimetry, pain during change of dressing measured on a visual analogue scale and adverse event assessment for tolerance. RESULTS: After 15 days the debridement rate in the active group was 67.5% compared to 59% in the placebo group (p = 0.0436). A significantly higher number of patients in the treatment group achieved 100% debridement by day 15 (p = 0.0025) than in the control group, and a higher percentage also demonstrated complete debridement at every other time point. Pain perception was similar in both groups with low levels during medication. No differences in tolerance were observed between groups. CONCLUSIONS: Chronic venous ulcers treated with this novel compound of Hyaluronic Acid and collagenase resulted in a significantly higher debridement rate at Day 15 vs. the control group. Hyaluronic Acid-Collagenase was well tolerated and a low degree of pain was perceived during dressing change. The preparation of 0.2% of Hyaluronic acid-collagenase shows significant benefits in the management of chronic ulcers.

A multi-centre, open label, long-term follow-up study to evaluate the benefits of a new viscoelastic hydrogel (Hymovis®) in the treatment of knee osteoarthritis.

OBJECTIVE: To evaluate the long-term efficacy and safety of Hymovis® in the symptomatic treatment of knee osteoarthritis (OA). PATIENTS AND METHODS: This is a prospective, multi-center, open label, phase III clinical study. Two intra-articular injections (3 mL) of Hymovis® (8 mg/mL HYADD® 4) were administered 1 week apart at the beginning of the study on day 0 and day 7 and after 6 months from baseline, on day 182 and 189. Follow-up assessment were conducted for 52 weeks. 50 subjects, > 40 years old, with knee OA, with clinical and radiological confirm, complain pain in the target knee were enrolled. The variables considered were: WOMAC questionnaire, Joint Space Width (JSW), OMERACT OARSI responder criteria, EQ-5D questionnaire, rescue medication consumption. RESULTS: After the injections of Hymovis®, pain perceived by the patient when walking on a flat surface (WOMAC A1 score) significantly improves at the end of the study respect to the baseline. WOMAC stiffness, physical function and total score significantly improve during the study since 3 months after treatment, and it is maintained up to the end of the study (p < 0.001). By the x-ray analysis of knee, a radiological progression of OA was observed in the 26% of patients at the end of the study, while 88% of patients result to be responder to the therapy classified as per OMERACT-OARSI criteria. The EQ-5D weighted index increased significantly, against baseline, at each study time point (p < 0.001). Investigator's and patient's global assessment of the disease measured by the VAS both show a marked improvement in patient's health conditions. CONCLUSIONS: Results from this study confirm that Hymovis® alleviate the knee pain since the first treatment cycle. The patients treated with two cycles of intra-articular injections of Hymovis® have a progressive pain reduction that is maintained up to one year after the treatment start with improve of all the scores considered in this study. Hymovis® is effective and safe in symptomatic treatment of painful knee OA.

Multicenter clinical trial on the performance and tolerability of the Hyaluronic acid-collagenase ointment for the treatment of chronic venous ulcers: a preliminary pilot study.

BACKGROUND: Bed debridement is important to treat chronic wounds. Effective agents should remove the necrosis but protect the granulation tissue. We evaluated the performance and tolerability of a new composite ointment containing collagenase and hyaluronic acid for chronic venous ulcers. PATIENTS AND METHODS: Subjects with class 6 venous ulcers (CEAP classification) of at least 6 months duration were prospectively recruited. The ointment was administered daily and follow-up visits were conducted on the fifth, 10th, 15th and 20th days. On each visit the necrotic area was measured with a grid. The moisture balance, odour, viability of non-necrotic areas and the presence of erythema were also assessed. Primary outcome was the percentage of subjects with complete debridement, secondary outcomes the time to complete healing, reduction of the lesion area, absence of necrotic tissue, presence of odor, erythema, hydration, any adverse events. RESULTS: One hundred subjects were enrolled in four centres. All patients achieved complete debridement of the necrotic area and a significant reduction of the total ulcer area by day 20, while other parameters improved significantly over time. Only two patients experienced a transient leg oedema. CONCLUSIONS: The combination of collagenase and hyaluronic acid is safe and effective for chronic venous ulcers.

A prospective observational study of the clinical efficacy and safety of intra-articular sodium hyaluronate in synovial joints with osteoarthritis.

BACKGROUND: Clinical trials have demonstrated the safety and efficacy of hyaluronic acid-based products for the treatment of synovial joints affected by osteoarthritis (OA), but data from observational studies of normal medical practice are sparse. AIM: This study investigated the safety and efficacy of intra-articular (IA) sodium hyaluronate (MW 1500-2000 KDa; Hyalubrix®) in the treatment of synovial joint OA. DESIGN: This is prospective, and observational study. SETTING: This study was carried out at 47 specialist centers for physiatrists, orthopedics and rheumatology in Italy; the enrolled population, 1266 outpatient, was predominantly female (66%, 840/1266), with a mean age of 66 years, and a mean weight of 74 kg. POPULATION: The Participants with OA received IA injections of the study treatment (2 mL) once per week for 3 weeks. The knee was the joint most commonly affected by OA (right knee 802/1266 [63%]; left knee 598/1266 [47%]), and the longest median duration of disease occurred in the carpal joint (right carpal joint 40 months; left carpal joint 60 months). METHODS: The primary endpoints were tolerability and details of usage of the IA sodium hyaluronate syringe device. Efficacy parameters included assessment of self-reported pain via the Visual Analogue Scale (VAS), and evaluation of motor function via the Health Assessment Questionnaire (HAQ). Quality of life (QoL) was assessed using the Euro QoL questionnaire (Clinical Trial Registration Number: ISRCTN 42690497). RESULTS: Data from 1266 participants were collected. The adverse event (AE) rate was 0.8% (95% CI, 0.4 to 1.5). Thirteen AEs were reported, 12 of which were mild or moderate in severity. Only one participant discontinued study treatment following an AE. No serious adverse events occurred. Coadministration of local anesthetic was required by up to 10% of patients. Statistically significant improvements in VAS, HAQ and EuroQoL were recorded in multiple joints (P<0.0001 for each). CONCLUSION: The study treatment was safe and well tolerated. CLINICAL REHABILITATION IMPACT: . The study treatment reduced pain, improved mobility, and increased QoL in participants with OA.