Multicenter Prospective Randomized Control Trial Research Articles

Abstract 10353: Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3 Year Results of the SUCCOUR Trial

Introduction: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction (CTRCD) and guide initiation of cardioprotection (CPT) at the time of chemotherapy. No prospective randomized controlled trial (RCT) has identified the impact on LV function in survivors. Hypothesis: GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care. Methods: In this international (28 sites) multicenter prospective RCT, patients (pts) were included if they were administrated anthracyclines and had another risk factor for HF. They were randomly allocated into undergoing GLS-guided CPT for >12% relative reduction in GLS or EF-guided CPT for >10% absolute reduction of EF. Primary endpoint was the change in EF (ΔEF) from baseline to 3 years by 3D echocardiography. Results: Among 331 pts enrolled, 255 (77%, 60±16 years, 95% women) completed 3-year follow-up (123 in EF-guided group and 132 in GLS-guided). Most had breast cancer (236, 93%), 67 (26%) with hypertension and 32 (13%) with diabetes mellitus. A regimen of anthracycline and trastuzumab was the most common chemotherapy regimen (84%). The baseline LVEF was 61±4% with GLS of 20.7±2.3% in the entire population. CPT was administrated in 18 pts (15%) in EF-guided and 41 (31%) in GLS-guided (p=0.02). Most patients showed recovery in EF and GLS after chemotherapy (Figure). ΔEF was -2.0±4.8 in EF-guided and -1.4±5.4 in GLS-guided (p=0.25), but LVEF at 3 years in EF-guided was lower than that of GLS-guided (58.0±5.6% vs 59±4.9%, p=0.043). Ten pts in EF-guided developed CTRCD, and 6 in GLS-guided (p=0.24). Conclusions: Most of the enrolled pts were taking potentially cardiotoxic chemotherapy for breast cancer. Almost all improved LV function over 3 years, and although GLS-guided CPT was associated with higher EF at 3 years, there was no difference in ΔEF compared with EF-guided surveillance.

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial

To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. The 52-week endothelial immune rejection rate. Ninety-two patients were randomized to receive bevacizumab (n= 48) or control (n= 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P= 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P= 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P= 0.01) in a post hoc Cox regression analysis. In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

Usefulness of an Accelerometer-Based Portable Navigation System for Total Knee Arthroplasty: A Multicenter Prospective Randomized Controlled Trial.

An accelerometer-based portable navigation system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter prospective randomized controlled trial (RCT) was to evaluate the effects of this accelerometer-based portable navigation system for achieving more accurate alignment during TKA in the clinical setting. One hundred patients with primary varus osteoarthritis of the knee were enrolled in this prospective RCT conducted in 5 hospitals. A navigation system was utilized in 50 patients (navigation group), and a conventional intramedullary femoral guide and an extramedullary tibial guide were utilized in 50 patients (conventional group). At 6 months postoperatively, weight-bearing radiographs were obtained of the whole operative leg. An experienced surgeon who was blinded to the treatment assignments then measured the alignment to 1 decimal place with use of computer software. Power analysis showed that 41 knees were required in each group. There were no complications as a result of the use of the accelerometer-based portable navigation system. Postoperative radiographs were obtained in 45 patients from each group. There were no significant differences in sex, age, height, body weight, body mass index, preoperative femorotibial angle, and operative time between groups. The absolute differences of the femoral prosthesis (p = 0.01), tibial prosthesis (p < 0.01), and hip-knee-ankle angle (p < 0.01) from a neutral mechanical axis were less in the navigation group compared with those in the conventional group. Alignment outliers (>2° away from the neutral mechanical axis) of the tibial prosthesis and hip-knee-ankle angle were less in the navigation group (9% and 27%, respectively) compared with those in the conventional group (31% and 49%; p = 0.01 and p = 0.04, respectively). To our knowledge, this is the first multicenter prospective RCT to evaluate an accelerometer-based portable navigation system. An accelerometer-based portable navigation system provides more accurate prosthetic and limb alignment in the coronal plane than conventional techniques, without extended operative time or an increased rate of complications. The results of this study may help orthopaedic surgeons decide whether or not to use an accelerometer-based portable navigation system. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Effect of an oral nutritional supplementation on nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy: A multi-center prospective randomized control trial

Objective: To evaluate the effect of oral nutritional supplementation (ONS) on the nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy. Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-13003798). A multi-center randomized controlled trial was conducted. Colorectal cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy, and had nutritional risk (nutrition risk screening 2002 score ≥3) when discharge from hospital in six hospitals (Beijing Hospital, Peking University Third Hospital, Guangzhou Nanfang Hospital, Shanghai Xinhua Hospital, Shanghai Ruijin Hospital, and Shanghai The Sixth People's Hospital) from June 2013 to August 2015 were prospectively enrolled. These patients were randomly divided into the ONS group and control group. Patients in the ONS group received dietary guidance and oral nutritional supplements (2092 kJ/day, whole protein enteral nutrition) for 90 days after discharge from hospital, while patients in the control group only received dietary guidance. Anthropometric measurements (body weight, body mass index [BMI], upper arm circumference, gripping power of the dominant hand, triceps skin fold), nutrition-related laboratory tests (hemoglobin, albumin, prealbumin, total cholesterol, triglyceride), gastrointestinal function scores and quality of life (evaluated by EuroQol five dimensions questionnaire) were collected and compared at baseline (at discharge), and at 30-day, 60-day and 90-day after discharge. Results: A total of 90 patients were included into this multi-center study, of whom 5 patients dropped out, 43 patients were assigned to the ONS group and 42 patients to the control group. Compared with baseline, the body weight of patients in the ONS group increased by (1.523±0.525) kg at 60-day and (1.967±0.661) kg at 90-day, which were significantly higher than those of patients in the control group [60-day: (-0.325±0.518) kg, P=0.015; 90-day: (-0.224±0.705) kg, P=0.027, respectively]. A similar pattern was observed for BMI, the ONS group increased by (0.552±0.203) kg/m(2) at 60-day and (0.765±0.205) kg/m(2) at 90-day, which were significantly higher than those of patients in control group [60-day: (-0.067±0.202) kg/m(2), P=0.034; 90-day: (0.022±0.210) kg/m(2), P=0.013]. No significant differences of other anthropometric measurements and nutrition-related laboratory tests were found between the two groups (all P>0.05). Furthermore, there were no significant differences of improvement in gastrointestinal function and quality of life between two groups (all P>0.05). Conclusion: Oral nutritional supplements can improve the body weight and BMI of colorectal cancer patients with nutritional risk receiving postoperative adjuvant chemotherapy, though it does not improve the quality of life.

GS-011 - Multicenter prospective randomized controlled trial comparing propranolol, endoscopic band ligation, and combination therapy for the primary prophylaxis variceal bleeding in patients with liver cirrhosis

GS-011 - Multicenter prospective randomized controlled trial comparing propranolol, endoscopic band ligation, and combination therapy for the primary prophylaxis variceal bleeding in patients with liver cirrhosis

Two-Year Outcomes from a Randomized Controlled Trial of Minimally Invasive Sacroiliac Joint Fusion vs. Non-Surgical Management for Sacroiliac Joint Dysfunction.

Sacroiliac joint (SIJ) dysfunction is an important and underappreciated cause of chronic low back pain. To prospectively and concurrently compare outcomes after surgical and non-surgical treatment for chronic SIJ dysfunction. One hundred and forty-eight subjects with SIJ dysfunction were randomly assigned to minimally invasive SIJ fusion with triangular titanium implants (SIJF, n = 102) or non-surgical management (NSM, n = 46). SIJ pain (measured with a 100-point visual analog scale, VAS), disability (measured with Oswestry Disability Index, ODI) and quality of life scores were collected at baseline and at scheduled visits to 24 months. Crossover from non-surgical to surgical care was allowed after the 6-month study visit was complete. Improvements in continuous measures were compared using repeated measures analysis of variance. The proportions of subjects with clinical improvement (SIJ pain improvement ≥20 points, ODI ≥15 points) and substantial clinical benefit (SIJ pain improvement ≥25 points or SIJ pain rating ≤35, ODI ≥18.8 points) were compared. In the SIJF group, mean SIJ pain improved rapidly and was sustained (mean improvement of 55.4 points) at month 24. The 6-month mean change in the NSM group (12.2 points) was substantially smaller than that in the SIJF group (by 38.3 points, p<.0001 for superiority). By month 24, 83.1% and 82.0% received either clinical improvement or substantial clinical benefit in VAS SIJ pain score. Similarly, 68.2% and 65.9% had received clinical improvement or substantial clinical benefit in ODI score at month 24. In the NSM group, these proportions were <10% with non-surgical treatment only. Parallel changes were seen for EQ-5D and SF-36, with larger changes in the surgery group at 6 months compared to NSM. The rate of adverse events related to SIJF was low and only 3 subjects assigned to SIJF underwent revision surgery within the 24-month follow-up period. In this Level 1 multicenter prospective randomized controlled trial, minimally invasive SIJF with triangular titanium implants provided larger improvements in pain, disability and quality of life compared to NSM. Improvements after SIJF persisted to 24 months. This study was approved by a local or central IRB before any subjects were enrolled. All patients provided study-specific informed consent prior to participation.

Sa1405 A Prospective Randomized Trial Comparing the 22-Gauge Needle With and Without a Side Port for Endoscopic Ultrasound Fine Needle Aspiration of Solid Pancreatic Mass Lesions

Sa1405 A Prospective Randomized Trial Comparing the 22-Gauge Needle With and Without a Side Port for Endoscopic Ultrasound Fine Needle Aspiration of Solid Pancreatic Mass Lesions Hirotoshi Ishiwatari*, Tsuyoshi Hayashi, Hiroshi Kawakami, Hiroyuki Isayama, Takao Itoi, Hiroyuki Hisai, Michihiro Ono, Yoko Abe, Natsuyo Yamamoto, Fumihide Itokawa, Tadashi Hasegawa Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Department of Gastroenterology, The University of Tokyo, Tokyo, Japan; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan; Department of Gastroenterology, Japanese Red Cross Date General hospital, Date, Japan; Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan Background: Endoscopic ultrasound fine needle aspiration (EUS-FNA) is widely used for obtaining specimens from pancreatic mass lesions, owing to its high diagnostic accuracy, safety, and low invasiveness. However, it remains imperfect and needs modification to enable accurate diagnosis. The 22-gauge (G) fine needle aspiration (FNA) needle is widely used owing to its maneuverability. However, a 19G needle is superior in terms of tissue acquisition. To overcome this limitation, 22G FNA needles with a lateral side port have been developed. The side ports initially had a reverse beveled edge. Recently, needles with a round side port have been developed, which may reduce tissue damage and blood contamination, and improve diagnostic yield. Preliminary results have shown high diagnostic accuracy. We compared 22G FNA needles with and without a side port in pancreatic mass lesions in a multicenter prospective randomized control trial. Patients and Method: Between January and September 2013, consecutive 160 patients with a suspected solid pancreatic mass in five tertiary referral centers were enrolled. Patients were randomized to 22G FNA needle (EZ Shot 2, Olympus Medical Systems) with and without a side port groups (with and without groups, respectively). The primary endpoint was diagnostic accuracy. The secondary endpoints were adequacy of tissue acquisition and quality of the histological specimen (degree of contamination and amount of blood). Evaluations were made using a scoring system, by experienced attending pathologists, who were blinded to the clinical information, including the needle type. Results: Analysis of 158 patients (79 per group) was performed. Two patients did not undergo EUS-FNA after allocation. In four patients (three in the with group and one in the without group), EUS-FNA failed owing to difficulty of the puncture. There was no significant difference in the diagnostic accuracy rate (with group, 92.4% (73/79) vs. without group, 86.1% (68/79); P Z 0.3, Fisher’s exact test). In subgroup analysis, trainees (endosonographers with experience of fewer than 40 EUS-FNAs) had diagnostic accuracy rates of 97.4% (37/38) and 81.4% (35/43) in the with and without groups, respectively (P Z 0.03, Fisher’s exact test). Adequate samples for histological diagnosis were obtained in 61.3% (47/76) and 44.2% (34/78) of patients from the with and without groups, respectively (P Z 0.03, Fisher’s exact test). No significant difference was seen in the degree of sample contamination and amount of blood between the groups. Conclusion: There was no significant difference in diagnostic accuracy between the needle types. However, the needle with a side port allowed trainees to obtain the correct diagnosis at a higher rate. Moreover, the needle with a side port is superior for tissue acquisition.(Clinical trial registration number: UMI08120)

Multicenter Prospective Randomized Study of Single-incision Mini-sling Vs Tension-free Vaginal Tape-obturator in Management of Female Stress Urinary Incontinence: A Minimum of 1-Year Follow-up

To compare an adjustable anchored single incision mini-sling (SIMS-Ajust) vs tension-free vaginal tape-obturator (TVT-O) in the management of female stress urinary incontinence (SUI) with a minimum of 1-year follow-up. We conducted a multicenter prospective randomized control trial (RCT) performed in 6 United Kingdom centers in the period between October 2009 and October 2011. Women were randomized to either SIMS-Ajust (C. R. Bard) performed under local anesthesia or TVT-O (Ethicon Inc.) performed under general anesthesia. Women completed validated symptom-severity and quality of life (QOL) questionnaires preoperatively and at 1 year. In addition, women completed the Patient Global Impression of Improvement (PGI-I) and underwent the Cough Stress Test (CST) at 1 year. The primary outcome at 12 months was the patient-reported success rate. Secondary outcomes included objective cure, reoperation rate, impact on women's urinary symptoms, QOL, and sexual function. Data was analyzed using SPSS-19 with significance level set at 5%. One hundred thirty-seven women were randomized into 2 groups: the SIMS-Ajust group (n=69) and the TVT-O group (n= 68). At 1 year, there were no significant differences in the patient-reported success rate (odds ratio [OR] 0.895, 95% confidence interval [CI] 0.344-2.330, P= 1.000), objectives success rate (OR 0.929, 95% CI 0.382-2.258, P= 1.00), and reoperation rates (OR 0.591, 95% CI 0.136-2.576, P= .721) between the SIMS-Ajust and the TVT-O groups, respectively. A comparable number of women reported cure/improvement of urgency (P= .658), significant improvement in QOL (P= .190), and sexual function (P= .699) in both groups. Adjustable-anchored SIMS (Ajust) is associated with comparable patient-reported and objective success rates when compared to standard midurethral sling (SMUS, TVT-O) at a minimum of 1-year follow-up. The results should be interpreted with caution due to the relatively small cohort size. Long-term follow-up of this RCT is required to ascertain the durability of these results.

Five-Year Follow-Up of the ProDisc-L Versus Fusion IDE Patient Cohorts

The multicenter prospective randomized control trial of single-level arthroplasty compared to anterior-posterior spinal fusion in patients with functionally-disabling discogenic back pain provided the clinical dataset for the PMA study leading to FDA-approval for ProDisc-L (TDR) in August 2006. The results of the two-year data has been previously published.

A comparison of outcomes between open and laparoscopic surgical repair of recurrent inguinal hernias

Inguinal hernia recurrence after surgical repair is a major concern. The authors report their experience with open and laparoscopic repair of recurrent inguinal hernias. After institutional review board approval, a retrospective review was performed with the charts of 197 patients who had undergone surgical repair of recurrent inguinal hernias from January 2000 through August 2009, and the data for 172 patients who met the inclusion criteria were analyzed. Surgical variables and clinical outcomes were compared using Student's t test, the Mann-Whitney U test, chi-square, and Fisher's exact test as appropriate. The review showed that 172 patients had undergone either open mesh repair (n=61) or laparoscopic mesh repair (n=111) for recurrent inguinal hernias. Postoperative complications were experienced by 8 patients in the open group and 17 patients in laparoscopic group (p=0.70). Five patients (8.2%) in the open group and four patients (3.6%) in the laparoscopic group had re-recurrent inguinal hernias (p=0.28). Four patients in the open group (9.5%) and no patients in the laparoscopic group had recurrence during long-term follow-up evaluation (p=0.046). In the laparoscopic group, 76 patients (68.5%) underwent total extraperitoneal (TEP) repair, and 35 patients (31.5%) had transabdominal preperitoneal (TAPP) repair. Postoperative complications were experienced by 13 patients in the TEP group and 4 patients in the TAPP group (p=0.44). Two patients (2.6%) in the TEP group and two patients (5.7%) in the TAPP group had re-recurrent inguinal hernias (p=0.59). This retrospective review showed no statistical difference in the re-recurrence rate between the two techniques during short-term follow-up evaluation. However, the laparoscopic technique had a significantly lower re-recurrence rate than the open technique during long-term follow-up evaluation. Both procedures were comparable in terms of intra- and postoperative complications. Among laparoscopic techniques, TEP and TAPP repair are acceptable methods for the repair of recurrent inguinal hernia. A multicenter prospective randomized control trial is needed to confirm the findings of this study.