Multicenter Post-marketing Study Research Articles

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Valvulotomy of the great saphenous vein in ex situ non-reversed and in situ setting: a multicenter post-market study to assess the safety and efficacy of the AndraValvulotome™”

PurposeTo evaluate the safety and technical success of the AndraValvulotome™ device (Andramed GmbH, Reutlingen, Germany) in patients with peripheral arterial disease (PAD) requiring bypass surgery using the great saphenous vein (GSV) as graft.MethodsThis was a multicenter, post-market observational study conducted in 2021 in 11 German centers. Safety and efficacy data were prospectively collected and analyzed. Primary endpoints were the absence of device-related serious adverse events until 30 ± 7 days follow-up, the clinical efficacy of valvulotomy, which was defined as pulsatile blood flow in the bypass and the number of insufficiently destroyed vein valves. Secondary endpoints were the number of valvulotomy passages, the primary patency rate of the venous bypass (determined by a color-duplex sonography showing a normal blood flow through the bypass and absence of stenosis or occlusion), and the primary technical success defined as the absence of product-specific (serious) adverse events and clinical efficacy.ResultsFifty-nine patients were enrolled. The mean age of the patients was 71 years (46–91), and 74.6% were males. The vein material used for bypass grafting had a median length of 47.5 cm (range 20–70 cm) with a median diameter of 5.0 mm (range 3–6 mm) and 4.0 mm (range 2–6 mm) in the proximal and distal segments, respectively. The technical success rate was 96.6%. The primary patency rate was 89.9% at 30 days follow-up. The clinical efficacy was rated as very good in 81% of patients, fair in 17%, and poor in 2%. Between 1 and 5 (average 2.9) valvulotome passages were performed. One product-related serious adverse event was recorded (bypass vein dissection).ConclusionThe AndraValvulotome™ can be considered a safe and effective device to disrupt venous valves during in situ non-reversed bypass surgeries using GSV grafts in patients with PAD.

Safety and effectiveness of tofogliflozin in elderly Japanese patients with type2 diabetes mellitus: A subanalysis of a post-marketing study (J-STEP/EL Study).

Aims/IntroductionThis subanalysis aimed to assess the safety and effectiveness of tofogliflozin by using data from the Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational Study of the Elderly to categorize elderly Japanese patients with type 2 diabetes mellitus by the number of concomitant oral antidiabetic drugs (OADs) and insulin use at baseline.Materials and MethodsJapanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational Study of the Elderly is a 1‐year prospective, observational and multicenter post‐marketing study that enrolled all patients with type 2 diabetes mellitus aged ≥65 years who started tofogliflozin during the first 3 months after its launch in May 2014 in Japan.ResultsThe safety and effectiveness analysis sets included 1,497 and 1,422 patients, respectively. Overall, 18.10 and 2.20% of the patients experienced adverse drug reactions (ADRs) and serious ADRs, respectively. ADRs of special interest in the total, 0 OAD, one OAD, two OADs, three or more OADs and insulin groups occurred in 12.22, 10.04, 12.35, 13.32, 11.27 and 14.91% of patients, respectively. Volume depletion‐related events were the most frequently observed ADRs of special interest. Hypoglycemia occurred in 1.07% of patients. Overall, glycated hemoglobin and bodyweight were significantly decreased, but the estimated glomerular filtration rate was not significantly changed.ConclusionsOur finding suggests that tofogliflozin could be safely and effectively used in elderly Japanese patients with type 2 diabetes mellitus, irrespective of the number of OADs and the use of insulin.

Safety and effectiveness of tofogliflozin in Japanese patients with type2 diabetes mellitus in real-world practice: Results of 12-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).

Aims/IntroductionDue to the paucity of tofogliflozin data, we assessed the safety and effectiveness of tofogliflozin among Japanese patients with type 2 diabetes mellitus in the clinical setting, stratifying the patients by age, sex, estimated glomerular filtration (eGFR) rate and body mass index. We report the results of a 12‐month interim analysis.Materials and MethodsThis was a 3‐year prospective, observational and multicenter post‐marketing study (Japanese Study of tofogliflozin with type 2 diabetes mellitus Patients/Long Term).ResultsOut of 6,897 patients enrolled, the safety and effectiveness analysis populations consisted of 6,712 and 6,449 patients, respectively. During 12 months, adverse drug reactions and their incidence were 9.12 and 0.88%, respectively. The incidence of hypoglycemia was 0.67%. Polyuria/pollakiuria occurred more frequently in patients aged ≥65 years than in patients aged <65 years. Women experienced higher rates of urinary tract and genital infection than men. The lowest eGFR subgroup experienced maximum volume depletion‐related events. Cardiovascular and cerebrovascular disorders occurred in 0.55% of the patients. Glycated hemoglobin (HbA1c) and bodyweight significantly decreased by −0.76% and −2.73 kg, respectively, from baseline to the last observation carried forward (P < 0.0001). Except for the lowest eGFR subgroup, other eGFR subgroups showed significantly decreased HbA1c values. All eGFR subgroups showed significantly decreased bodyweight, and all body mass index subgroups showed significantly decreased HbA1c and bodyweight.ConclusionsOur interim 12‐month data suggest that tofogliflozin could be used safely and effectively in Japanese patients with type 2 diabetes mellitus, as tofogliflozin was well tolerated with low hypoglycemia risk, and significantly improved HbA1c and bodyweight.

Small-aperture strategies for the correction of presbyopia.

The recent scientific literature provides evidence of long-term results with small-aperture corneal inlays, as well as new evidence from a multicenter postmarket study of small-aperture intraocular lenses (IOLs) and early reports of the use of topical agents for presbyopia correction through pupil constriction. The field of small-aperture optics is growing and changing rapidly. This article reviews what is known to date about various small-aperture optics platforms, including a posterior chamber IOL, add on device, corneal inlay, contact lenses, and pupil-constricting drops. Additionally, the impact of small-aperture technologies on light perception and visual performance, as well as the relative merits of monocular versus binocular small apertures are discussed. Small-aperture optics are a dynamic, physiologic solution to the problem of presbyopia. They are effective throughout the range of accommodation loss and in pseudophakia. Small-aperture optics offer an opportunity to improve vision in presbyopes with and without cataracts. In some forms, they may also be able to reduce the impact of aberrations or improve vision in eyes with corneal irregularities, scars, or iris damage.

MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population.

Patients with ischemic cardiomyopathy (ICM) are prone to scar-related ventricular tachycardia (VT). The success of VT ablation depends on accurate arrhythmogenic substrate localization, followed by optimal delivery of energy provided by constant electrode-tissue contact. Current manual and remote magnetic navigation (RMN)-guided ablation strategies aim to identify a reentry circuit and to target a critical isthmus through activation and entrainment mapping during ongoing tachycardia. The MAGNETIC VT trial will assess if VT ablation using the Niobe™ ES magnetic navigation system results in superior outcomes compared to a manual approach in subjects with ischemic scar VT and low ejection fraction. This is a randomized, single-blind, prospective, multicenter post-market study. A total of 386 subjects (193 per group) will be enrolled and randomized 1:1 between treatment with the Niobe ES system and treatment via a manual procedure at up to 20 sites. The study population will consist of patients with ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) of ≤35% and implantable cardioverter defibrillator (ICD) who have sustained monomorphic VT. The primary study endpoint is freedom from any recurrence of VT through 12months. The secondary endpoints are acute success; freedom from any VT at 1year in a large-scar subpopulation; procedure-related major adverse events; and mortality rate through 12-month follow-up. Follow-up will consist of visits at 3, 6, 9, and 12months, all of which will include ICD interrogation. The MAGNETIC VT trial will help determine whether substrate-based ablation of VT with RMN has clinical advantages over manual catheter manipulation. Clinicaltrials.gov identifier: NCT02637947.

VTI InterFuse® S vs. InterFuse® T for the treatment of scoliosis and degenerative disc disease: protocol for a multicenter post-market study

Background and objectives: VTI InterFuse® S and InterFuse® T are the interbody fusion devices used in spinal fusion procedures to relieve the pain of patients with scoliosis and degenerative disc disease through maintaining foraminal height and decompression. The aim of this study is to investigate the therapeutic effects of the VTI InterFuse® S and InterFuse® T on scoliosis and degenerative disc disease. Design: A prospective, two-arm, multicenter, post-market trial. Methods: A total of 200 eligible patients (18-19 years old) with scoliosis and/or degenerative disc disease and a planned fusion of at least 5 levels were recruited from 10 clinical sites. The patients will be assigned to receive T interbody fusion treatment with the InterFuse® S or InterFuse® interbody fusion devices. Outcome measures: The following outcome measures will be observed during 24-month follow-up: interbody fusion assessed by CT scan (primary outcome measure), and Visual Analog Scale and Oswestry Disability Index, and the Scoliosis Research Society Outcomes Instrument scores (secondary outcome measures). Discussion: This study will provide direct evidence for the intelligent use of VTI InterFuse® S and InterFuse® T interbody fusion devices in the treatment of scoliosis and/or degenerative disc disease. Ethics and dissemination: The study will receive approval from the institutional review board at each site and will be conducted in accordance with the ethical principles of the Declaration of Helsinki. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals. Trial registration: ClinicalTrials.gov identifier: NCT02659722 on January 15 th , 2016.

Correction: VTI InterFuse® S vs. InterFuse® T for the treatment of scoliosis and degenerative disc disease: protocol for a multicenter post-market study

Correction: VTI InterFuse^® S vs. InterFuse^® T for the treatment of scoliosis and degenerative disc disease: protocol for a multicenter post-market study

Abstract P1-10-02: Usage of epoetin alfa biosimilars in the management of chemotherapy-induced anemia in patients with breast cancer: A subanalysis of the ORHEO study

Abstract Introduction Chemotherapy-induced anemia (CIA) is a frequent complication of breast cancer patients that is associated with fatigue and impaired quality of life. Biosimilars of erythropoietin-stimulating agents have now been approved to treat CIA in Europe. The ORHEO (biOsimilaRs in the management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was an observational study conducted in France to evaluate the efficacy and safety of a biosimilar epoetin alfa in an oncology setting. The large number of patients who enrolled in the study permitted indication-specific subanalyses to be undertaken. Herein we report the results of the subanalysis that focuses on the subpopulation of breast cancer patients. Methods The ORHEO study was a prospective, observational, longitudinal, multicenter postmarketing study. Patients ≥18 years with CIA (hemoglobin [Hb] &amp;lt;11 g/dL)-associated solid tumors, lymphomas, or myelomas who were eligible for treatment with an epoetin alfa biosimilar were enrolled. The primary endpoint was Hb response (defined as Hb reaching ≥10 g/dL, an increase of Hb ≥1 g/dL since inclusion, or reaching target Hb) measured at 3 and 6 months (M3 and M6, respectively). Secondary endpoints included safety and tolerability. Only breast cancer patients with CIA were included in this subanalysis. Results The ORHEO study enrolled 2333 patients; of these, 266 patients presented with CIA associated with breast cancer and were included in this subanalysis. The mean age was 61 years, the majority had ECOG PS 1 (51.5%) and metastatic disease (56.0%), and 99.6% received an epoetin alfa biosimilar. At baseline, the mean Hb level was 9.9 g/dL. At the M3 and M6 time points, an Hb response was observed in 86.8% and 91.7% of patients, respectively; average Hb levels increased by 1.3 g/dL (M3) and 1.8 g/dL (M6). By M3, 44% of patients reached their target Hb level; this increased to 53.7% at M6. At M3 and M6, of those patients who definitively or temporarily discontinued treatment, over half did so because the target Hb had been reached (M3: 55.6% [n = 74/133]; M6: 53.2% [n = 81/152]). Clinically significant adverse events (AEs) were observed in 9.9% of patients; the most common AE was infection (7.9%), while thrombotic events were only reported in 0.8% of patients. High baseline systolic blood pressure, high hematocrit levels at M3, and clinical improvement by M3 were identified as potential indicators of a positive response to an epoetin alfa biosimilar. Conclusion This subanalysis of the large ORHEO observational study has demonstrated the utility of biosimilar epoetin alfa in a real-world setting. Biosimilar epoetin alfa was seen to be efficacious and well tolerated in patients with breast cancer who presented with CIA, and no new safety signals were identified in this subpopulation. These data support the results observed in the parent ORHEO study, and confirm that biosimilar epoetin alfa (Hospira) is a therapeutic alternative for treating CIA in patients with breast cancer. Several potential prognostic indicators were identified that may warrant further study. Citation Format: Albrand H, Luporsi E, Michallet M, Soubeyran P. Usage of epoetin alfa biosimilars in the management of chemotherapy-induced anemia in patients with breast cancer: A subanalysis of the ORHEO study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-02.

OFLOMELID OINTMENT: CLINICAL AND LABORATORY EFFICACY AND TOLERABILITY IN PATIENTS WITH SKIN AND SOFT TISSUE INFECTIOUS PROCESSES

The paper presents the results of a multicenter postmarketing study of Oflomelid ointment versus levosin and levomecol ointments in 301 patients with different purulent diseases of the skin, soft tissues, and bones, diabetic foot syndrome, trophic ulcers of different etiologies, postoperative purulent wounds, chronic posttraumatic osteomyelitis, burns and frostbites, acute and chronic purulent diseases of the skin and soft tissues. Oflomelid ointment shows a high clinical and bacteriological efficacy in stages I and II wound process along with good analgesic activity for the topical treatment of purulent processes of different etiologies and sites. Objectivization of the findings is based on the results of qualitative and quantitative microbiological analyses, wound imprint cytology, and trends in the systemic and local clinical picture.

The real-life experience with fingolimod in Mexico: a multicenter post-marketing study

The real-life experience with fingolimod in Mexico: a multicenter post-marketing study

Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study

Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

Use of frameless intrauterine devices and systems in young nulliparous and adolescent women: results of a multicenter study.

BackgroundThe purpose of this study was to provide additional data on the experience with frameless copper and levonorgestrel (LNG) intrauterine devices (IUDs) in nulliparous and adolescent women.MethodsNulliparous and adolescent women, 25 years of age or younger, using the frameless copper IUD or the frameless LNG-releasing intrauterine system (IUS), were selected from previous studies and a current multicenter post-marketing study with the frameless copper IUD. The small copper-releasing GyneFix® 200 IUD consists of four copper cylinders, each 5 mm long and only 2.2 mm wide. The frameless FibroPlant® LNG-IUS consists of a fibrous delivery system releasing the hormone levonorgestrel (LNG-IUS). The main features of these intrauterine contraceptives are that they are frameless, flexible, and anchored to the fundus of the uterus.ResultsOne hundred and fifty-four nulliparous and adolescent women participated in the combined study. One pregnancy occurred with the GyneFix 200 IUD after unnoticed early expulsion of the device (cumulative pregnancy rate 1.1 at one year). Two further expulsions were reported, one with the GyneFix 200 IUD and the other with the FibroPlant LNG-IUS. The cumulative expulsion rate at one year was 1.1 with the copper IUD and 2.2 with the LNG-IUS. The total discontinuation rate at one year was low (3.3 and 4.3 with the copper IUD and LNG-IUS, respectively) and resulted in a high rate of continuation of use at one year (96.7 with the copper IUD and 95.7 with the LNG-IUS, respectively). Continuation rates for both frameless copper IUD and frameless LNG-IUS remained high at 3 years (>90%). There were no cases of perforations or pelvic inflammatory disease reported during or following insertion.ConclusionThis report confirms earlier studies with frameless devices and suggests that the high user continuation rate is attributable to the optimal relationship between the IUD and the uterine cavity. IUD studies have shown that an IUD that does not fit well will often lead to side effects (ie, pain, bleeding, embedment, expulsion) and subsequent removal of the IUD. Early discontinuation is not the aim of long-acting reversible contraception.

Clinical effects of micafungin, a novel echinocandin antifungal agent, on systemic fungal infections in surgery, emergency, and intensive-care medicine: evaluation using the AKOTT algorithm

The clinical efficacy of micafungin (MCFG) in surgery, emergency, and intensive-care medicine has been studied in only a limited number of cases. We conducted a multicenter postmarketing study to evaluate MCFG efficacy and safety in Japan. MCFG was given to patients with a temperature exceeding 37.5 degrees C, either with a proven fungal infection based on mycological or histopathological examination, or those who were regarded as having probable or possible fungal infections (patients who had at least one high-risk factor for the development of a systemic fungal infection and for whom fungi had been detected at multiple sites by surveillance culture or a positive beta-D-glucan test). Efficacy was evaluated using the AKOTT algorithm created by our group (AKOTT is an acronym created from the first letter of the surname of each of the five members of the evaluation committee). Of the 180 patients enrolled, 68 were excluded by exclusion criteria or for other reasons, and 112 (58 with proven candidiasis, 1 with proven aspergillosis, and 53 with suspected fungal infection) were evaluated for efficacy. MCFG was administered at a mean daily dose of 104 mg for a mean duration of 14.2 days. It was effective in 72 p 72 patients, ineffective in 28, and the effect was undeterminable in 12, for an overall clinical efficacy 72.0%. MCFG was effective in 78.6% of those with proven candidiasis and in 65.1% with suspected fungal infection, but it was ineffective in the 1 patient with aspergillosis. MCFG eradicated 77.6% (52/67) of fungi isolated. There were 69 drug-related adverse reactions, mainly abnormal hepatic function tests, in 37 of 178 patients evaluated for safety. One adverse reaction, skin eruption, had a probable causal relationship with drug treatment. In conclusion, MCFG had high clinical efficacy and safety in the treatment of deep-seated fungal infections in surgery, emergency, and intensive-care medicine, indicating good potential as a firstline drug for both targeted and empirical therapies.

Postmarketing experience with topiramate and cognition.

Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double-blind, placebo-controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open-label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment. We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with "better" or "much better" ratings of both seizure and global improvement during treatment.

The PROTECT study: final results of a large multicenter postmarketing study in patients with type 2 diabetes

The Precose ® Resolution of Optimal Titration to Enhance Current Therapies (PROTECT) trial was a nationwide postmarketing study designed to assess the effectiveness, tolerability, and safety of acarbose in patients with type 2 diabetes mellitus. This prospective, multicenter, open-label, 28-week trial enrolled 6142 patients who had type 2 diabetes that was inadequately controlled with either diet alone or diet plus a sulfonylurea. The dosage of acarbose was titrated from 25 mg TID to 50 mg TID (forced titration) and then titrated from 50 mg TID to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic control was assessed by recording changes in glycated hemoglobin A 1c (Hb A 1c) and 1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were determined on the basis of patients' reports of treatment-emergent adverse events and by review of laboratory test results. Acarbose was safe and effective in improving glycemic control in patients with type 2 diabetes, regardless of their age, weight, ethnic background, time since diagnosis, or concomitant sulfonylurea therapy. HbA 1c levels declined throughout the treatment period, for a mean change in Hb A 1c of −0.66%. The mean change from baseline in 1-hour PPG levels was −41 mg/dL at the end of treatment. Although all types of patients enrolled in the study responded positively to acarbose therapy, certain subgroups responded particularly well, especially those who had been diagnosed with the disease for less than 1 year and those who were untreated at study entry. Adverse events consisted primarily of gastrointestinal disturbances