key: cord-0744124-6k3du30j authors: Phillips, Edward; Ponce, Jaime; Bhoyrul, Sunil; Cunneen, Scott A.; Gomez, Eddie; Jacobs, Moises; Kipnes, Mark; Marema, Robert T.; Schwiers, Michael; Waggoner, Jason R.; DeMarchi, Janet title: Safety and Effectiveness of REALIZE™ Adjustable Gastric Band: 5-year Prospective Study date: 2021-01-22 journal: Surg Obes Relat Dis DOI: 10.1016/j.soard.2021.01.019 sha: c4089cd52cfb889278c3d5e33d444973cedee0b2 doc_id: 744124 cord_uid: 6k3du30j BACKGROUND: The long-term safety results of the REALIZE (Ethicon Endo-Surgery, Inc., Cincinnati, OH) Adjustable Gastric Band collected in this prospective, multi-center study in subjects with morbid obesity are presented. The primary objective was to determine the reoperation rate, including band revision, replacement and explant resulting from a serious adverse device-related event through years four and five. Various efficacy measures were also assessed as secondary objectives. METHODS: Nine academic and/or private institutions enrolled 303 subjects who were then assessed on an annual basis. Two hundred thirty-one subjects completed five years of follow-up. The study parameters included reoperation rates, changes in percentage of Excess Weight Loss (%EWL), Body Mass Index (BMI) as well as parameters of diabetes and dyslipidemia. Quality of life was assessed using SF-36 and the Impact of Weight on Quality of Life (IWQOL-Lite) questionnaires. RESULTS: The reoperation rate due to a serious adverse event in this population at five years after implantation with the REALIZE gastric band was 8.9%. The most common serious adverse event was band slippage which affected 6.9% of the study population. The mean %EWL was 35.6 + 26.84 and the decrease in mean BMI was -7.01 + 5.45 at 5 years. Subjects experienced improvement in mean hemoglobin A1c and serum lipid levels in addition to improvement in the quality of life measures. CONCLUSION: No new safety concerns were identified during the five years of follow up. Although the results of this study did not meet the predefined safety criteria of 8% or less, the safety profile and long-term effectiveness observed in this study is consistent with the current literature. According to the World Health Organization (WHO), the worldwide prevalence of obesity has tripled since 1975 [1] . It is estimated that, in 2016, there were 1.9 billion adults (age 35 18+) who were overweight and 650 million adults who were obese [1] . Obesity is associated with a wide variety of undesirable health outcomes. Being overweight or obese substantially raises an individual's risk of mortality and morbidity from hypertension, dyslipidemia, type 2 diabetes (T2DM), coronary heart disease, stroke, gall bladder disease, osteoarthritis, sleep apnea, respiratory problems, and endometrial, breast, prostate, and colon cancers [2] . In a more recent 40 development, obesity, especially for those patients with a BMI >35, is a contributing factor to the severity of SARS-CoV-2 and the need for invasive mechanical ventilation [3] . Evidence has demonstrated that various strategies to reduce weight in overweight and obese individuals can successfully reduce the risks of mortality and morbidity. [2, [4] [5] [6] Weight exhibit the most substantial and durable response among the available weight loss interventions. However, weight loss surgeries are major operations with certain limitations and with both shortand long-term complications. The purpose of this study is to present 5-year safety and effectiveness data for the 50 REALIZE gastric band (manufactured by Ethicon Endo-Surgery, Inc.), as directed by the United States (US) Food and Drug Administration (FDA). The primary objective was to assess the 5- year REALIZE gastric band reoperation rate, including band revision, replacement, and explantation resulting from a serious adverse device-related event (SADE). The secondary (effectiveness) objectives were to evaluate changes in excess weight, quality of life (QoL), 55 hemoglobin A1c (HbA1C), and serum lipid levels five years after implantation of the REALIZE gastric 60 Nine academic and/or private practice clinical sites were selected to participate in the study, based on their laparoscopic surgery experience and multidisciplinary team approach. All study centers followed a common protocol approved by their respective institutional review boards. This was a prospective, single-arm, multi-center study to fulfill the FDA requirement to perform a post approval study to evaluate long term safety and effectiveness of the REALIZE Adjustable Gastric Band (clinicaltrials.gov: NCT 00543140). The initial study included 140 subjects who had the device implanted under the original Pre-Market Approval (PMA) protocol J o u r n a l P r e -p r o o f (clinicaltrials.gov: NCT 00166205) who were re-consented into the extension. An additional 163 70 enrolled in a parallel protocol for a total of 303 in the Intent to Treat population (ITT). Data was pooled from all protocols and conducted under similar conditions using the same device to assess safety and efficacy at the same assessment periods. A total of 231 (76.2%) subjects completed the five-year follow-up visit. The final study visit was completed on January 12, 2015. Male and female subjects between 18 and 60 years of age (inclusive) who were considered appropriate 75 candidates for a surgical weight loss intervention (Body Mass Index (BMI) of > 40 kg/m 2 and ≤ 55 kg/m 2 , or BMI ≥ 35 kg/m 2 and < 40 kg/m 2 with one or more comorbid conditions) were considered for inclusion in both the initial PMA and extension cohort as well as the parallel post market study cohort. Key exclusion criteria for the PMA extension group included: The REALIZE™ Adjustable Gastric Band also known as the Swedish Adjustable Gastric Band (SAGB) or the Curved Adjustable Gastric Band (Ethicon Endo-surgery, Cincinnati OH) were implanted in accordance with their respective Instructions for Use. The surgical technique has been previously described by Phillips, et al. [7] . The sample size was selected to provide greater than 80% power, based on a one-sided exact binomial test and a 0.05 significance level, to detect a significant difference from the performance goal of 8% after 4 and 5 years of implantation. The performance goal of 8% was 105 based upon the safety results of the initial three years of this study and also with input from FDA. The reoperation rate in years 1-3 was ~2% per year, projected to 4% for years 4 and 5. Doubling this rate established a 8% performance goal based upon an inferiority margin factor of 2.Secondary effectiveness parameters were summarized by-year post implantation. For continuous parameters, descriptive statistics including mean, standard deviation, median, 110 minimum, maximum and 95% confidence intervals of the mean. Change from baseline was summarized in a similar manner with baseline defined as the last available measurement on or before the date of implantation. Analysis of the SF-36 Questionnaire and IWQOL-Lite was consistent with the recommendations for these surveys and the significance of change from J o u r n a l P r e -p r o o f baseline was assessed using the matched pairs t-test. Categorical parameters were summaries 115 with counts and percentages. The disposition of subjects showing the merging of the two cohorts is presented in There were nine participating institutions that contributed to this study. Table 1 lists the site numbers, the number of subjects enrolled and the number of subjects who completed 60 months 125 of follow up. Seventy-two of the 303 subjects did not complete the 5-year visit. The reasons for study discontinuation are listed in Table 2 130 The complications or Serious Adverse Events prompting device removal included devicerelated infection, band slippage, erosive gastritis due to band erosion and impaired gastric emptying. There was one subject death in the study, during the second year of follow up, due to myocardial infarction, deemed unrelated to the study device or procedure. The demographics and baseline characteristics of the combined study population are presented in Table 3 . The majority 135 of subjects were female and Caucasian, not of Hispanic origin, with a mean age of 40.5 years. The combined study population had a mean weight of 272.2 pounds, mean BMI was 44.1 kg/m 2 and mean waist circumference was 49.2 inches. Of the 303 subjects enrolled, 76 (25.1%) experienced at least 1 serious adverse event over the course of the study. Table 4 lists the most common serious adverse events reported over the five years of follow-up and the number of subjects affected. The primary safety endpoint was reoperation rate, defined as the reoperation rate using the number of subjects for whom reoperations were performed during years 4 and 5 as the numerator, and the number of subjects included in that population (intent to treat (ITT)) as the denominator. For the purpose of this study, reoperations were defined as band explantation, band 150 revision and band replacement, resulting from a serious adverse device-related event. There were 27 qualified reoperations that fit the protocol definition for a rate of 8.9% (27/303) with a 95% confidence interval (CI) range of 6.0 to 12.7% (p= 0.6919 for comparison to < 8%). As mentioned previously, one death occurred during this study, due to myocardial infarction, considered unrelated to the REALIZE gastric band device or procedure. While not the focus of this study, effectiveness parameters were collected and are summarized in Table 5 . When considering A1c values, of the 303 enrolled subjects, 16.2% (49/303) met the 160 definition of having diabetes with an A1c >6.5 or a medical history diagnosis of Type II diabetes at the beginning of the study, decreasing to 8.6% of subjects over the duration of the study. The mean A1c of this diabetic subgroup was 7.8 (range 6.4 -11.9) at baseline, decreasing to 7.2 (range 5.4 -11.5) at last evaluable visit. Of these 49 subjects, 46.9% experienced (23/49) a drop in A1c to less than 6.5 from an average of 7.5 to 5.85. Fourteen subjects (28.6%) showed 165 improvement but remained at or above the 6.5 threshold at the last evaluable study visit. The The secondary effectiveness results seen in this study demonstrate that there is a reasonable assurance that, in a significant portion of the target population, the use of the device for its intended use and conditions of use will provide clinically significant effectiveness results. The need for additional surgical intervention is of high concern to the long-term utility of an adjustable gastric band for weight loss. The primary goal of this study was to determine the reoperation rate (band revision, band replacement, and explantation resulting from SAEs) of 190 gastric banding at Years 4 and 5 after implantation. The safety success criterion for this study was an observed device-related reoperation rate that was 8% or less for Years 4 and 5 of the study. This post-market safety study had a reoperation rate of 8.9% with a 95% CI range of 6.0% to 12.7%. Even though this study failed to meet its safety success criterion, the safety performance of the REALIZE gastric band illustrated in this study was acceptable and consistent In this multicenter study, mean %EWL across all sites ranged from 22.58 + 14.54 to 52.44 + 27.20. Table 6 shows the number of subjects per site who completed the five year follow up and the corresponding mean %EWL. No discernible trends were apparent regarding mean %EWL at 60 months and the percentage of subjects completing the study. In the original Premarket Approval study, the mean %EWL at 3years post-surgery was 41.2%, [7] which is similar to that seen in this post-market extension study (i.e., 41.2%). This and other similarities are an indication of the validity of merging the 215 populations reported herein. Table 4 lists the complete weight loss and lab value results. In the present study, the mean reduction in absolute weight at 5-years post-surgery was -43.1 ± 32.5 pounds while the mean percentage in weight reduction at 5-years post-surgery was 16.0 ± 11.9%. This translated to a mean reduction in BMI of -7.0 ± 5.45 kg/m 2 at 5-years post-surgery. In comparison to similar studies, the 5-year post surgery mean %EWL of 35.6 with a 220 BMI change of -7.0 suggests that the benefits of LAGB are durable as well as repeatable. Similarly, Vitiello, et al [11] , noted a mean %EWL of 40.5 at 5 years and a BMI change of -9.36. In a recent study, O'Brien et al, [12] in a large, long-term LAGB population study (n=5235), showed a mean %EWL of 47.7 with a reduction in BMI of 8.5 points at 5 years. Improvements in various metabolic factors were maintained at 5-years post-surgery. Mean described in the 3-year study. In the 49 patients meeting the definition of being diabetic with an A1c of > 6.5% or a medical history diagnosis of Type II diabetes, almost half (46.9%) reduced their A1c to non-diabetic levels during the study. In addition to an acceptable reoperation rate, %EWL and improvements in metabolic factors, these changes were accompanied by lasting improvements in QOL at 5-years post-surgery based on SF-36 Physical Component and domain scores and total transformed score and domain scores for the IWQOL-Lite. There were several limitations in this investigation. There was no comparison group but the subject functioned as his/her own control with results pre-and post-treatment. The results of this study may not be generalizable to clinical practice as the study was done in specialized centers and may not represent all sites of care. Twenty-four percent of the population (72/303) did not complete the entire study for various reasons, with the most common being lost to follow 240 up. This post-market safety study had a reoperation rate of 8.9%, which did not meet the arbitrary, pre-determined safety success criterion of 8%. Even so, the general safety profile, J o u r n a l P r e -p r o o f Vomiting defined as forcible loss of stomach contents deemed related to the study device. c Hiatal hernia defined as a protrusion of the upper stomach through the diaphragm into the chest cavity. J o u r n a l P r e -p r o o f Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation Review of meta-analytic comparisons of bariatric surgery with a focus on 275 laparoscopic adjustable gastric banding Impact of laparoscopic adjustable gastric banding on obesity co-morbidities in the medium-and long-term Systematic review of medium-term weight loss after bariatric operations Safety and effectiveness of REALIZE adjustable gastric band: 3 year 285 prospective study in the United States Management of failed adjustable gastric banding Laparoscopic adjustable gastric banding on 3566 patients up to 20-year follow-up: Long-term results of a standardized The authors wish to acknowledge professional medical writing services from Natalie Edwards.