Multicenter Pivotal Study Research Articles

Sunvozertinib for the treatment of NSCLC with EGFR Exon20 insertion mutations: The first pivotal study results.

9002 Background: Sunvozertinib(DZD9008) is a rationally designed selective, irreversible EGFR exon20 insertion (exon20ins) inhibitor with wild-type EGFR selectivity. Here we reported the results of WU-KONG6, the first pivotal study of sunvozertinib in previously treated NSCLC patients with EGFR exon20ins. Methods: WU-KONG6 (NCT05712902 and CTR20211009) is a phase II, multi-center pivotal study in NSCLC patients with EGFR exon20ins, whose diseases had progressed on or were after platinum-based chemotherapy. Tumor tissue EGFR exon20ins status was tested by local or central laboratory. The primary and key secondary endpoint were objective response rate (ORR) and duration of response (DoR), respectively, assessed by Blinded Independent Central Review (BICR). Patients received 300 mg sunvozertinib once daily until discontinuation criteria were met. Results: Between July 19, 2021, and May 6, 2022, a total of 104 Chinese patients were enrolled into WU-KONG6 study. The efficacy analysis set included 97 patients, whose EGFR exon20ins status was retrospectively confirmed by a central laboratory. A total of 30 different exon20ins subtypes were enrolled. The median age was 58 years; 59.8% (58/97) were female; 95.9% (93/97) were adenocarcinoma; 95.9% (93/97) had metastatic diseases at study entry; 32% (31/97) had baseline brain metastasis; the median prior lines of therapy were 2. By the data cutoff date (October 17, 2022), the BICR assessed confirmed ORR (cORR) was 60.8% (59/97). In patients with baseline brain metastasis, the cORR was 48.5% (15/31). Anti-tumor efficacy was observed irrespective of age, gender, smoking status, prior lines of therapies, prior onco-immunotherapies, mutation subtypes, and baseline brain metastasis. By the data cut-off date, median follow-up time for responders was 7.1 months, and 64.4% (38/59) of responders were still responding. The longest DoR was > 11 months, and the median DoR has not been reached. The safety analysis set included all enrolled 104 patients. The most common treatment emergent adverse events (TEAEs) were similar as what have been previously reported for sunvozertinib, and also similar as that of other EGFR inhibitors. Majority of the TEAEs were grade 1 or 2, and clinically manageable. Conclusions: The first pivotal study results confirmed sunvozertinib’s superior anti-tumor efficacy than the current available therapy for NSCLC with EGFR exon20ins. The safety profile from WU-KONG6 study was consistent with previously reported findings. The updated data will be presented at the meeting. A multinational phase II pivotal study (WU-KONG1, NCT03974022) with the same study design is ongoing in the USA, Australia, and countries/regions in Asia, Europe and South America. Clinical trial information: NCT05712902 .

Colorectal Cancer and Polyp Detection Using a New Preparation-Free, Colon-Scan Capsule: A Pilot Study of Safety and Patient Satisfaction.

Current strategies to prevent colorectal cancer (CRC) vary considerably regarding safety, invasiveness, and patient satisfaction. A known deterrent for patients is the required bowel cleansing for colonoscopy. A new colon-scan capsule system is a unique preparation-free approach that provides structural information on colonic mucosa intended for detection of colorectal polyps and masses. The aim of this study was to determine safety and patient satisfaction with the colon-scan capsule. Prospective single-arm pilot study conducted at two tertiary care centers. Patients with a pre-scheduled colonoscopy for CRC screening or surveillance were included. Patients participating in this study underwent the colon-scan capsule and colonoscopy. Safety was defined by the occurrence of procedure or device-related adverse events. Satisfaction was based on survey questionnaires using a scoring system 1 (strongly disagree) to 5 (strongly agree). Patient satisfaction with the colon-scan capsule was compared to colonoscopy. Forty patients were included (52.9 [5.7] years; 64.1% females). There were no serious adverse events and no occurrences of capsule retention. The most common (12.5%) complaint was self-limiting abdominal cramping. Satisfaction questionnaires were completed by more than 87% of patients, with patients likely to recommend the capsule (score 4.1 [1.03]) compared to colonoscopy (score 2.8 [1.2]), p = 0.001. The new prepless colon-scan capsule system is an innovative, minimally invasive technology with demonstrated safety and high patient satisfaction. A multicenter pivotal study is planned to validate the performance, safety, and accuracy of polyp detection using the capsule system in comparison with colonoscopy.

70-OR: Evaluation of the Omnipod 5 Automated Insulin Delivery System in Very Young Children with Type 1 Diabetes (T1D)

The Omnipod 5 System is a novel hybrid closed-loop (HCL) system with full on-body operation. A tubeless insulin pump containing a personalized MPC algorithm communicates directly with a Dexcom G6 CGM to automate insulin delivery. Following demonstration of positive safety and efficacy in older children (≥6y) and adults, we evaluated the system in very young children (2-5.9y) with T1D. Preschoolers with T1D often have erratic eating behaviors and may dislike being tethered to devices, and parental concern may lead to permissive hyperglycemia. This HCL system may be ideal for young children, given its customizable glucose targets from 110-150mg/dL, wireless system interaction through a mobile application, and bolus calculator that incorporates CGM trend information. Also, the system has no minimum weight or total daily dose (TDD) requirement. Participants with T1D and A1C<10% used their respective standard therapies (ST) for 14d, and then transitioned to use of the HCL system for 3mo. Primary safety outcomes are the incidence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA). Primary effectiveness outcomes are change in A1C and percent of time in target range (TIR, 70-180 mg/dL) with the HCL system compared with ST. Baseline characteristics of participants (N=80) were (mean±SD) age 4±1y (range 2-5y), T1D duration 2.2±1.1y, and A1C 7.4±0.9%, with mean (range) TDD 13.7 (5.3-27.1) U/day and weight 20 (12-53) kg. There have been no serious adverse events, including SH and DKA, reported in over 5,254 person-days of HCL use. During the ST phase, TIR was 57.2±15.1%, time <54mg/dL was 0.8±1.7%, <70mg/dL was 3.4±3.9%, >180mg/dL was 39.4±16.5%, and ≥250mg/dL was 14.7±12.0%. The same efficacy analysis is planned for the 3-month HCL phase upon its completion in January 2021. This multi-center pivotal study has, to date, demonstrated safety of the Omnipod 5 System in very young children with T1D. At completion, this will be the largest study of HCL in this age group reported to date. Disclosure J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic, Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Speaker’s Bureau; Self; Lilly Diabetes. D. W. Hansen: None. T. T. Ly: Employee; Self; Insulet Corporation. Omnipod 5 in preschoolers study group: n/a. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtronic, Nova Biomedical, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanofi, Senseonics, Viacyte, Inc., vTv Therapeutics, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; Self; AgaMatrix, Aseko, Inc., Glytec, LLC. G. P. Forlenza: Advisory Panel; Self; Medtronic, Consultant; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. S. A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A. B. Criego: Consultant; Self; Bigfoot Biomedical, Inc., Other Relationship; Self; Sanofi, Research Support; Self; Abbott Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. Funding Insulet Corporation

Safety Evaluation of the Omnipod® 5 Automated Insulin Delivery System Over Three Months of Use in Children With Type 1 Diabetes (T1D)

Advances in diabetes technology have transformed the treatment paradigm for T1D, yet the burden of the disease remains significant. The pediatric population poses unique challenges to glucose management with unpredictable exercise and food consumption. The Omnipod 5 System is a novel hybrid closed-loop (HCL) system with fully on-body operation. A tubeless insulin pump (pod) containing a personalized Model Predictive Control algorithm communicates directly with a Dexcom G6 continuous glucose monitor (CGM, or sensor) to automate insulin delivery. Therapy customization is enabled through glucose targets from 110–150 mg/dL, adjustable by time of day, which is a critical component to individualize glucose management in children. We report on the first, pivotal outpatient safety evaluation of the Omnipod 5 System in a large cohort of children with T1D.Participants aged 6–13.9y with T1D≥6 months and A1C<10% used the HCL system for 3 months at home after a 14-day run-in phase of their standard therapy (ST, included both pump therapy and multiple daily injections). The primary safety and effectiveness endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and change in A1C and sensor glucose percent time in target range (TIR) (70–180 mg/dL) during HCL compared with ST.Participants (N=112) were aged (mean±SD) 10.3±2.2y with T1D duration 4.7±2.6y and baseline A1C 7.7±0.9% (range 5.8–10.3%). TIR increased significantly from ST to HCL, from 52.5±15.6% to 68.0±8.1% (p<0.0001), corresponding to an additional 3.7 hours/day in target range. A1C at end of study was reduced by 0.7% to 7.0±0.6% (p<0.0001). Percentages of time in hyperglycemia were reduced: >180 mg/dL from 45.3±16.7% to 30.2±8.7% and ≥250 mg/dL from 19.1±13.1% to 9.6±5.4% (both p<0.0001). Percentages of time in hypoglycemia remained low from ST to HCL: <54 mg/dL from 0.4±0.8% to 0.3±0.3% and <70 mg/dL from 2.2±2.7% to 1.8±1.4% (both p>0.05). Mean glucose decreased from 183±32 to 160±15 mg/dL (p<0.0001). During the HCL phase there was 1 episode of SH (delayed eating after pre-meal bolus) and 1 episode of DKA (suspected infusion site failure) reported. Virtually all participants completing the pivotal study (99%) continued system use during an extension phase.In this multi-center pivotal study in a large cohort of children with T1D, the Omnipod 5 System was safe and effective when used for 3 months at home. There were significant improvements in both TIR and A1C, while time below range (<70 mg/dL) remained low. The beneficial glycemic outcomes are critical for children, given that neurologic outcomes can be negatively impacted by hyperglycemia. The current results and commitment to the extension phase emphasize the safe and effective use of the HCL system, as well as the preference for the Omnipod 5 System over participants’ previous therapy.

Safety Evaluation of the Omnipod® 5 Automated Insulin Delivery System Over Three Months of Use in Adults and Adolescents With Type 1 Diabetes (T1D)

Abstract Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes (T1D), yet the burden of disease remains significant. The Omnipod 5 Automated Insulin Delivery System is a novel hybrid closed-loop (HCL) system with fully on-body operation. The system consists of a tubeless insulin pump (pod) containing a personalized Model Predictive Control algorithm which communicates directly with a Dexcom G6 continuous glucose monitor (CGM, or sensor) to automate insulin delivery. Therapy customization is enabled through glucose targets from 110-150 mg/dL, adjustable by time of day. The system adapts to changing insulin needs with each pod change. We report on the first, pivotal outpatient safety evaluation of the system in a large cohort of adults and adolescents with T1D. Participants aged 14-70y with T1D≥6 months and A1C&amp;lt;10% used the HCL system for 3 months at home after a 14-day run-in phase of their standard therapy (ST). Prior therapy included both pump therapy and multiple daily injections. The primary safety and effectiveness endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and change in A1C and sensor glucose percent time in target range (TIR) (70-180 mg/dL) during HCL compared with ST. Participants (N=128) were aged (mean±SD) 37±14y with T1D duration 18±12y and baseline A1C 7.2±0.9% (range 5.2-9.8%). There was a significant increase in TIR from ST to HCL, from 64.7±16.6% to 73.9±11.0% (p&amp;lt;0.0001), corresponding to an additional 2.2 hours/day in target range. A1C at end of study was reduced by 0.4%, from 7.2±0.9% to 6.8±0.7% (p&amp;lt;0.0001). Glycemic outcomes for percent of time with CGM readings below and above target range were all reduced (p&amp;lt;0.0001): &amp;lt;54 mg/dL from 0.6±1.2% to 0.2±0.3% (a decrease of 6 minutes/day), &amp;lt;70 mg/dL from 2.9±3.1% to 1.3±1.1% (a decrease of 23 minutes/day), &amp;gt;180 mg/dL from 32.4±17.3% to 24.7±11.2% (a decrease of 1.8 hours/day), and ≥250 mg/dL from 10.1±10.5% to 5.8±5.5% (a decrease of 1.0 hours/day). The mean glucose also decreased from 161±28 to 154±17 mg/dL (p=0.0002). During the 3-month HCL phase there were 2 episodes of SH (both following user-initiated boluses) and no episodes of DKA reported. Most participants completing the pivotal study (92%) opted to continue using the system during an extension phase. In this outpatient, multi-center pivotal study in a large cohort of adults and adolescents with T1D, the Omnipod 5 System was safe and effective when used for 3 months at home. There were significant improvements in both TIR and A1C with use of the system, while time in hypoglycemic ranges was also reduced. The current results and commitment to the extension phase highlight the safe and effective use of the HCL system, as well as the preference for the Omnipod 5 System over participants’ previous therapy.

Multicenter pivotal study of the safety and effectiveness of a tissue stabilized-guided subcision procedure for the treatment of cellulite: 5 year update

Multicenter pivotal study of the safety and effectiveness of a tissue stabilized-guided subcision procedure for the treatment of cellulite: 5 year update

730 - Performance evaluation of bladder EpiCheckTM for NMIBC monitoring: European multi-center pivotal study

730 - Performance evaluation of bladder EpiCheckTM for NMIBC monitoring: European multi-center pivotal study

A Multicenter Pivotal Study to Evaluate Tissue Stabilized-Guided Subcision Using the Cellfina Device for the Treatment of Cellulite With 3-Year Follow-Up.

Cellulite is a common female cosmetic concern for which no single treatment option had been proven effective over the long term. A novel tissue stabilized-guided subsicion system (TS-GS system) has demonstrated significant reduction in the appearance of cellulite after treatment. The objective of this extended follow-up period was to assess the effectiveness of TS-GS out to 3 years after initial treatment. After completing an open-label, multicenter, pivotal study, 45 subjects were followed for an extended period of up to 3 years after receiving a single treatment using the TS-GS system. Treatment areas were photographed prior to the procedure and at multiple time points post-treatment throughout the 3 years. In this open-label study, subjects served as their own controls. Effectiveness was assessed based on blinded independent physician panel assessments of improvement from baseline using a cellulite severity scale. Subject aesthetic improvement and patient-reported satisfaction were also collected. The results of this trial supported Food and Drug Administration clearance of the device for the long-term reduction in the appearance of cellulite following TS-GS. These data further demonstrate the safety and efficacy of this treatment with no reduction in treatment benefits out to 3 years.

PHASE I/II STUDY OF BRENTUXIMAB VEDOTIN IN REFRACTORY/RELAPSED HODGKIN LYMPHOMA PATIENTS TREATED BY CHEMOTHERAPY (ICE) IN SECOND LINE BEFORE AUTOLOGOUS TRANSPLANTATION.

Introduction: About 10–15% of patients with localized and 25–30% with disseminated classical HL failed to respond or relapse after primary conventional treatment. Autologous stem cell transplantation (ASCT) is a standard of care after salvage chemotherapy leading to an increased disease free survival (DFS). With this strategy approximately 60% to 80% of patients proved to be chemo sensitive become eligible for ASCT. As the disease status before ASCT appears to be the most important factor predicting outcome, second line chemotherapy has to be more efficient. Brentuximab-Vedotin (BV), a CD30-directed antibody conjugated to the highly potent anti-microtubule agent monomethyl auristatin E (MMAE), has shown significant activity in a phase II single arm, open label, multicenter pivotal study (SG035-0003) in patients with relapsed or refractory HL, of whom 71% had primarily refractory disease. Given the above, it seems to be logical and feasible to use BV in patients treated with ICE before auto SCT to induce a significantly higher (metabolic) CR rate, as judged by FDG-PET negativity. Otherwise, Moskowitz et al. have reported that negativity of FDG-PET improves EFS (>80% compared with 28.9% for those patients with improvement of CT but with persistent PET positivity). Methods: In order to increase the complete response (CR) rate judged by FDG-PET in patients with primary refractory or first relapse cHL, we added Brentuximab Vedotin to ICE (Ifosfamide, carboplatine, and etoposide) chemotherapy (ICE-BV). In the first dose-finding part of the study (phase I), the optimal dose of BV with ICE (3 cycles) will be established. In the second part the efficacy of BV with ICE will be assessed at the fixed optimal dose level of both BV and ICE. Results: Phase I study was activated in 5 centers of the LYSA group and 10 patients have already been enrolled. Patients received 3 cycles of ICE-BV and one cycle of BV before ASCT. Three patients were enrolled in the first cohort, BV: 1.2 mg/kg and 7 patients in cohort two (BV: 1.8 mg/kg). Clinical characteristics at inclusion were median age: 29.5 years (range: 22–55), sex ratio (M/F): 6/4, and status of the disease: refractory: 3 patients and relapse: 7 patients. Efficacy and toxicity are currently analyzed. Conclusion: The first part of ICE-BV before ASCT in R/R HL patients has been completed. Phase II will start after the validation of BV dose by the Independent Data Monitoring Committee (IDMC). Keywords: brentuximab vedotin; classical Hodgkin lymphoma (cHL); ICE.

Tissue Stabilized-Guided Subcision for the Treatment of Cellulite: A Multicenter Pivotal Study With Two-Year Follow-up.

Tissue Stabilized-Guided Subcision for the Treatment of Cellulite: A Multicenter Pivotal Study With Two-Year Follow-up.

LAP-BAND for BMI 30–40: 5-year health outcomes from the multicenter pivotal study

We performed a 5-year multicenter study to evaluate the safety and effectiveness of the LAP-BAND System surgery (LBS) in patients with obesity with a body mass index (BMI) of 30-39.9 kg m(-)(2). This pivotal study was designed to support LBS application to the US Food and Drug Administration for broadening the indications for surgery and the lower BMI indication was approved with 1-year data in 2011, with the intention to complete the 5-year evaluation. To present broad health outcome data including weight change, patient reported outcomes, comorbidity change and complications during the 5-year study. The study was conducted at seven US private practice clinical trial sites. We enrolled 149 BMI 30-39.9 subjects into a 5-year, multicenter, longitudinal, prospective post-approval study. Data for those completing each time point are presented. The predefined target of at least 30% excess weight loss was achieved by more than 76% of subjects by 1-year and at every year thereafter during the 5-year study. Mean percentage weight loss at 5 years was 15.9±12.4%. Sustained weight loss was accompanied by sustained improvement in generic and weight-specific quality of life, symptoms of depression and the prevalence of binge-eating disorder. The number of subjects with normal fasting triglyceride, high-density lipoprotein cholesterol, plasma glucose and HbA1c increased significantly between baseline and 5 years. Fifty-four months after LBS implantation, the rate of device explants without replacement was 5.4%; however, the rate of explants increased to 12.1% by month 60 owing to no cost-elective band removals offered to subjects at study exit. No deaths or unanticipated adverse device effects were reported. The LBS is safe and effective for people with BMI 30-39.9 with demonstrated improvements in weight loss, comorbidities and quality of life, and with a low explant rate through 5 years following treatment.

Multicenter pivotal study of the safety and effectiveness of controlled tissue release for the treatment of cellulite

Multicenter pivotal study of the safety and effectiveness of controlled tissue release for the treatment of cellulite

A New-Generation Continuous Glucose Monitoring System: Improved Accuracy and Reliability Compared with a Previous-Generation System

Use of continuous glucose monitoring (CGM) systems can improve glycemic control, but widespread adoption of CGM utilization has been limited, in part because of real and perceived problems with accuracy and reliability. This study compared accuracy and performance metrics for a new-generation CGM system with those of a previous-generation device. Subjects were enrolled in a 7-day, open-label, multicenter pivotal study. Sensor readings were compared with venous YSI measurements (blood glucose analyzer from YSI Inc., Yellow Springs, OH) every 15 min (±5 min) during in-clinic visits. The aggregate and individual sensor accuracy and reliability of a new CGM system, the Dexcom(®) (San Diego, CA) G4™ PLATINUM (DG4P), were compared with those of the previous CGM system, the Dexcom SEVEN(®) PLUS (DSP). Both study design and subject characteristics were similar. The aggregate mean absolute relative difference (MARD) for DG4P was 13% compared with 16% for DSP (P<0.0001), and 82% of DG4P readings were within ± 20 mg/dL (for YSI ≤ 80 mg/dL) or 20% of YSI values (for YSI >80 mg/dL) compared with 76% for DSP (P<0.001). Ninety percent of the DG4P sensors had an individual MARD ≤ 20% compared with only 76% of DSP sensors (P=0.015). Half of DG4P sensors had a MARD less than 12.5% compared with 14% for the DSP sensors (P=0.028). The mean absolute difference for biochemical hypoglycemia (YSI <70 mg/dL) for DG4P was 11 mg/dL compared with 16 mg/dL for DSP (P<0.001). The performance of DG4P was significantly improved compared with that of DSP, which may increase routine clinical use of CGM and improve patient outcomes.

Immunogenicity of osteogenic protein 1: results from a prospective, randomized, controlled, multicenter pivotal study of uninstrumented lumbar posterolateral fusion

The aim in this study was to detect and quantify antibody responses against recombinant human osteogenic protein 1 (OP-1) and to compare these responses to patient clinical outcomes and safety information. A controlled, open-label, randomized, prospective, multicenter pivotal study was performed in which patients with single-level Grade I or II degenerative lumbar spondylolisthesis (Meyerding classification) and spinal stenosis underwent decompression and uninstrumented posterolateral spinal arthrodesis. Three hundred thirty-six patients were randomized in a 2:1 fashion to receive either OP-1 Putty or autogenous iliac crest bone graft. Patients were evaluated at regular postoperative intervals for radiographic results, clinical outcomes, and safety parameters for more than 36 months. Serum samples were collected over this period and evaluated for the presence of anti–OP-1 antibodies and neutralizing activity by using a battery of in vitro binding assays (including enzyme-linked immunosorbent assay [ELISA]) and cell-based bioassays, respectively. Antibodies were predominantly seen in the OP-1–treated patients, although some responses were recorded preoperatively and in patients receiving autograft alone. Antibody production peaked in the 6-week to 3-month postoperative time frame and diminished thereafter. Neutralizing antibodies (Nabs) were detected at 1 time point at least in 25.6% of the patients treated with OP-1 Putty, but were not found in any patient following the 24-month postoperative time period. A single autograft patient (1.2%) also presented with OP-1 Nabs. An anti–OP-1 antibody status did not correlate with any measure of patient outcomes or adverse events. Recombinant human OP-1 (bone morphogenetic protein 7), like many recombinant human proteins, induces an immune response following its use as a bone graft alternative. This response was transient and diminished over time, and there was no statistical evidence to suggest an association between Nab status and any of the efficacy or safety criteria that were examined.

Results of the U.S. Multicenter Pivotal Study of the HELEX Septal Occluder for Percutaneous Closure of Secundum Atrial Septal Defects

This study sought to compare the safety and efficacy of the HELEX septal occluder (HSO) with surgical repair of atrial septal defect (ASD). The HSO is a low-profile, double-disk occluder device for percutaneous closure of secundum ASD. Patients were enrolled (HSO arm prospectively, surgery arm prospectively/retrospectively) from 14 U.S. sites and followed up for 12 months postprocedure. Investigator-reported outcomes were evaluated, including closure success (no or clinically insignificant residual shunt) and the incidence of adverse events. The first 3 HSO patients at each site were considered training cases and were excluded from analysis. Between March 2001 and April 2003, 119 nontraining cases received an HSO and 128 had surgical repair. The groups were similar with statistical but clinically unimportant differences in median age, weight, and preprocedural echocardiographic defect size. Anesthesia time and hospital stay were significantly shorter in the HSO group. Closure success, defined as complete closure or a clinically insignificant residual shunt, was similar in both groups. Major and minor adverse events rates were not statistically different. The most common major adverse events for the HSO group was device embolization requiring catheter retreival (1.7%), and in the surgery group was postpericardiotomy syndrome (6.3%), including one death because of tamponade. The primary end point, clinical success, a composite of closure success and no major adverse events at 12 months, satisfied the noninferiority hypothesis comparing device closure with surgery. Closure of ASD with the HELEX septal occluder is safe and effective when compared with surgical repair, with reduced anesthesia time and hospital stay. (U.S. Multicenter Pivotal Study of the HELEX Septal Occluder for Percutaneous Closure of Secundum Atrial Septal Defects; this study was approved by the Food and Drug Administration before the National Institutes of Health website was active, so there is not a URL or registration number.).