Characteristics of pivotal clinical trials of FDA-approved endovascular devices between 2000 and 2018: An interrupted time series analysis.

Background: The Food and Drug Administration (FDA) reviews safety, efficacy, and the quality of medical devices through its regulatory process. The FDA Safety and Innovation Act (FDASIA) of 2012 was aimed at accelerating the regulatory process for medical devices. Objectives: The purpose of our study was to (1) quantify characteristics of pivotal clinical trials (PCTs) supporting the premarket approval of endovascular medical devices and (2) analyze trends over the last two decades in light of the FDASIA. Methods: We surveyed the study designs of endovascular devices with PCTs from the US FDA pre-market approval medical devices database. The effect of FDASIA on key design parameters (e.g., randomization, masking, and number of enrolled patients) was estimated using an interrupted time series analysis (segmented regression). Results: We identified 117 devices between 2000-2018. FDASIA was associated with a decrease in double blinding (p < 0.0001) and a decrease in historical comparators (p < 0.0001). Discussion: Our results reveal an overall trend of decreased regulatory requirements as it relates to clinical trial characteristics, but a compensatory increased rate of post-approval across device classes. Furthermore, there was an emphasis on proving equivalence or non-inferiority rather than more use of active comparators in clinical trials. Medical device stakeholders, notably clinicians, must be aware of the shifting regulatory landscape in order to play an active role in promoting patient safety.

Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism.

BACKGROUND: Evidence supporting interventional pulmonary embolism (PE) treatment is needed. AIMS: We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE in a large real-world population. METHODS: FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement. RESULTS: Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m2 mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001).  Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.

Percutaneous Biliary Endoscopy for Stones.

Intraductal biliary stones can result in significant acute and long-term complications. When patients' anatomy precludes more traditional management, the interventional radiologist may be called upon to provide well-established techniques for percutaneous biliary drainage and stone removal. This can be particularly challenging when the patient has excessively mobile, impacted, large or multiple stones. Percutaneous biliary endoscopy with adjunct interventional techniques can successfully treat these patients avoiding the patient dreaded "tube for life" scenario. Direct percutaneous visualization of the biliary tree can also diagnose and provide symptomatic relief for stone-mimicking pathologic conditions such as biliary tumors. This article will review the role, technique, and considerations for percutaneous biliary endoscopy and adjunct interventions in patients with isolated and complex, biliary stone disease and stone-mimicking pathologies.

Safety and efficacy of venoplasty in MS: A randomized, double-blind, sham-controlled phase II trial.

OBJECTIVE: To determine the safety and efficacy of balloon vs sham venoplasty of narrowing of the extracranial jugular and azygos veins in multiple sclerosis (MS). METHODS: Patients with relapsing or progressive MS were screened using clinical and ultrasound criteria. After confirmation of >50% narrowing by venography, participants were randomized 1:1 to receive balloon or sham venoplasty of all stenoses and were followed for 48 weeks. Participants and research staff were blinded to intervention allocation. The primary safety outcome was the number of adverse events (AEs) during 48 weeks. The primary efficacy outcome was the change from baseline to week 48 in the patient-reported outcome MS Quality of Life-54 (MSQOL-54) questionnaire. Standardized clinical and MRI outcomes were also evaluated. RESULTS: One hundred four participants were randomized (55 sham; 49 venoplasty) and 103 completed 48 weeks of follow-up. Twenty-three sham and 21 venoplasty participants reported at least 1 AE; one sham (2%) and 5 (10%) venoplasty participants had a serious AE. The mean improvement in MSQOL-54 physical score was +1.3 (sham) and +1.4 (venoplasty) (p = 0.95); MSQOL-54 mental score was +1.2 (sham) and -0.8 (venoplasty) (p = 0.55). CONCLUSIONS: Our data do not support the continued use of venoplasty of extracranial jugular and/or azygous venous narrowing to improve patient-reported outcomes, chronic MS symptoms, or the disease course of MS. CLINICALTRIALSGOV IDENTIFIER: NCT01864941. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with MS, balloon venoplasty of extracranial jugular and azygous veins is not beneficial in improving patient-reported, standardized clinical, or MRI outcomes.

Ureteral Interventions.

Interventional radiologists are commonly called upon to manage patients with benign and malignant ureteral pathologic conditions. Unfortunately, treatments for both cure and palliation can be fraught with problems causing patients to be undesirably maintained with lifelong catheters. This review describes outcomes for antegrade and retrograde therapeutic options and techniques for patients with most types of ureteral pathologic conditions that the interventional radiologist would encounter in practice.

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases.

PURPOSE: There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver. PATIENTS AND METHODS: A total of 93 patients were randomized to PHP-Mel (n = 44) or BAC (n = 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4-8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety. RESULTS: hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (p < 0.0001), while oPFS was 5.4 months for PHP-Mel and 1.6 months for BAC (p < 0.0001). Median OS was not significantly different (PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (p < 0.001). The majority of adverse events were related to bone marrow suppression. Four deaths were attributed to PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC. CONCLUSION: This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.

The ABCs of the FDA: A Primer on the Role of the United States Food and Drug Administration in Medical Device Approvals and IR Research.

The role of the US Food and Drug Administration (FDA) in medical device regulation is important to device-driven specialties such as interventional radiology. Whether it is through industry-sponsored trials during the approval process for new devices or investigator-initiated research prospectively evaluating the role of existing devices for new or established procedures, interaction with the FDA is an integral part of performing significant research in interventional radiology. This article reviews the potential areas of interface between the FDA and interventional radiology, as understanding these areas is necessary to continue the innovation that is the hallmark of this specialty.

Comparison of COMPUTED TOMOGRAPHY Image Quality Using Intravenous vs. Intraosseous Contrast Administration in Swine.

BACKGROUND: Vascular access is essential in managing patients with significant injuries. It is required for medications, fluids, blood products, and radiographic contrast administration. Generally, this is accomplished through peripheral intravenous (i.v.) cannulation. In some patients, however, i.v. cannulation may be difficult or impossible. Intraosseous (i.o.) access is an acceptable alternative for many uses during resuscitation. However, adequacy of vascular enhancement with i.o. administration of contrast has not been studied. OBJECTIVES: This study was performed to assess the efficacy of i.o. administration of contrast agents for enhanced computed tomography (CT) imaging of the chest and abdomen. METHODS: We carried out a crossover study in mature mini-swine with peripheral i.v. and i.o. access established. Intraosseous access was obtained in the proximal humerus with fluoroscopic confirmation. Each animal underwent two trauma-protocol CT scans successively using the i.v. or i.o. routes of contrast administration. Wash-out between studies was established. The order for route of administration was randomized. Images were evaluated for adequacy of enhancement by two blinded board-certified radiologists. RESULTS: All images obtained with successful administration of i.o. contrast were judged adequately enhanced, whereas two from the i.v. route were judged to be inadequate by at least one of the radiologists. Two occurrences of failed i.o. needle placement occurred. One animal had complete contrast extravasation resulting in inadequate opacification. CONCLUSIONS: In this model, injection of contrast through a proximal humerus i.o. resulted in adequate enhancement of trauma-protocol CT images. Our results suggest that i.o. administration of contrast merits further investigation of its potential utility in patients when i.v. access would delay diagnostic evaluation.

Subcutaneous implantable cardioverter defibrillator for dialysis patients: a strategy to reduce central vein stenoses and infections.

Central venous stenosis is a common complication of the transvenous leads associated with an implantable cardioverter defibrillator (ICD). Although epicardial leads have been reported to bypass this complication, their placement is much more invasive than the subcutaneous ICDs (SICDs) and requires the services of a cardiothoracic surgeon. Recent data have demonstrated successful defibrillation using an SICD. In this report, we present 4 long-term hemodialysis patients treated successfully with an SICD. 3 patients received the device for primary prevention of sudden cardiac death (cardiomyopathy with low ejection fraction). The patient in the fourth case had a prolonged QT interval and received the device for secondary prevention. 3 patients had an arteriovenous fistula, whereas 1 patient was dialyzing with a tunneled dialysis catheter. Insertion of an SICD is a minimally invasive procedure. By virtue of leaving the venous system untouched, this approach might offer the advantage of reduced risk of central venous stenosis and infection over an endocardial ICD with transvenous leads. SICD is not experimental; it has been approved by the US Food and Drug Administration and is currently being used in the United States and Europe.

Management of splenic trauma: a single institution's 8-year experience.

BACKGROUND: Management of splenic trauma has evolved, with current practice favoring selective angiographic embolization and non-operative treatment over immediate splenectomy. Defining the optimal selection criteria for the appropriate management strategy remains an important question. METHODS: This retrospective registry review was conducted at a Level I trauma center. The patient population consisted of 20,561 patients in the State Trauma Registry from April 2004 to May 2012. Splenectomy, angiography, splenic embolization, nonoperative, and noninterventional (NI) observation were the management strategies under study. Morbidity and mortality were the outcome measures. Morbidity and mortality by management strategy. RESULTS: During the 8-year study period, 926 (4.5%) patients sustained splenic injury. Observational management increased over time despite the similar distribution of splenic injury grade over the study period: grade I/II (50%), grade III (24.2%), and grade IV/V (25.8%). Mortality rates associated with each management strategy were the following: immediate splenectomy (IS; 25%), splenic embolization (SE; 3.9%), and angiography only or observation, that is, NI (6.5%) management. Injury severity score (ISS) was highest in IS (36.1 ± 1.3) compared with SE (29.1 ± 1.0, P = .001) and NI (21.6, P < .001). Splenectomy was required in 5 of the 129 (3.9%) patients managed with SE and 9 of the 677 (1.3%) patients managed by NI. Mortality was significantly lower among those managed by SE (odds ratio .12, 95% confidence interval: .05 to .32) or NI (odds ratio .21, 95% confidence interval: .12 to .35). This survival benefit was explained by the association of IS with systolic blood pressure <90, high ISS, low GCS at presentation, ISS, development of shock, need for transfusion, and multiorgan failure. CONCLUSIONS: In this large 8-year single institution study, we observed an increase in nonoperative management by an increased application of angiography and embolization. An aggressive utilization of SE in patients with appropriate indications will result in low failure rates and improved mortality.

Renal artery stenosis: to intervene, or not to intervene, "that is the question".

Renal artery stenosis (RAS) due to atherosclerosis continues to be a major cause of secondary hypertension. It can also lead to renal dysfunction due to ischemic nephropathy. While major clinical trials have emphasized that medical management should be preferred over angioplasty and stenting for the treatment of renal artery stenosis, clinical scenarios continue to raise doubts about the optimal management strategy. Herein, we present two cases that were admitted with hypertensive emergency and renal function deterioration. Medical therapy failed to control the blood pressure and in one patient, renal failure progressed to a point where renal replacement therapy was required. Both patients underwent angioplasty (for >90% stenosis) and stent insertion with successful resolution of stenosis by interventional radiology. Postoperatively, blood pressure gradually decreased with improvement in serum creatinine. Dialysis therapy was discontinued. At 4- and 8-month follow-up, both patients continue to do well with blood pressure readings in the 132-145/70-90 mmHg range. This article highlights the importance of percutaneous interventions in the management of atherosclerotic RAS and calls for heightened awareness and careful identification of candidates who would benefit from angioplasty and stent insertion.

Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study.

PURPOSE: To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. METHODS: 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. RESULTS: Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. CONCLUSION: Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated.

Blood pressure recordings during hemodialysis access interventions: implications for acute management.

A retrospective study evaluating the pattern of blood pressure and its related complications before, during, and after percutaneous hemodialysis interventions was performed in patients presenting with asymptomatic hypertension. Hemodialysis patients undergoing percutaneous interventions including tunneled hemodialysis catheter insertion, percutaneous balloon angioplasty and thrombectomy procedure, and stage II hypertension (systolic blood pressure ≥160 mmHg) were included in this analysis. Blood pressure medications were not used while midazolam and fentanyl were routinely administered. Patients were followed for up to 4 weeks to monitor any complications. The mean blood pressure before, during, and after the procedures were 185 ± 18/96 ± 14, 172 ± 22/92 ± 15, and 153 ± 25/87 ± 14, respectively. There was a statistically significant difference between the blood pressure readings before and after the procedure (before = 185 ± 18/96 ± 14, after = 153 ± 25/87 ± 14; p = 0.001). None of the patients had a stroke, myocardial infarction, or acute pulmonary edema before, during, or after the procedure or during the 4-week follow-up period. A significant reduction in blood pressure was observed after the procedure without the administration of any antihypertensive medication. These results suggest that the reduction in blood pressure observed after percutaneous dialysis access interventions (particularly in the presence of midazolam and fentanyl) may make it unnecessary to treat asymptomatic hypertension prior to these procedures.

A prospective postmarket study to evaluate the safety and efficacy of a new peripherally inserted central catheter stabilization system.

An initial postmarket study of the SecurAcath used with 5 Fr peripherally inserted central catheters (PICCs) was conducted with 68 adult patients at 3 different institutions in the United States. PICCs were placed in both outpatients and inpatients, with patients in critical care and medical/surgical units, home care, and extended care facilities. Sixty-two (91.2%) of the patients completed therapy without a securement-related device malfunction or device-related adverse event associated with the securement system. The device was readily accepted by both patients and nursing staff. The SecurAcath represents a novel, safe, and effective method for catheter securement.

Radial artery harvest: a potential cause of arteriovenous access-associated hand ischemia.

Hand ischemia has multiple causes. In this article, we report an additional factor that can induce hand ischemia in hemodialysis patients. A 64-year-old white man with coronary artery disease underwent a coronary artery bypass graft procedure using the left radial artery as the bypass graft. Several months later, a left extremity Gracz fistula was created for arteriovenous access. Ever since dialysis was performed via the fistula the patient has experienced a cold hand and pain during dialysis that was somewhat relieved by wearing a woolen glove while on dialysis. Absence of the radial artery in the context of an ipsilateral arteriovenous access was highlighted as a possible etiology. A complete arteriography to determine the presence of stenoses, distal arteriopathy, and true steal was recommended, but the patient refused to undergo any investigation or procedure and instead decided to continue wearing the glove during the treatment. A plan for close follow-up and possible interventions in the event of worsening pain/ulceration was agreed upon. Radial artery harvest can result in hand ischemia if an ipsilateral arteriovenous access is created. We suggest that the contralateral extremity should be considered if an arteriovenous access is required to minimize this risk of this phenomenon.