Transitioning a randomized controlled trial to a digital registry – experience from the TAILOR-PCI digital follow-up study on onboarding, engagement and geofencing consent rate

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Avram ◽  
D So ◽  
E Iturriaga ◽  
J Byrne ◽  
R.J Lennon ◽  
...  
Keyword(s):  
Clinical Trial ◽  
The United States ◽  
Mobile App ◽  
Funding Source ◽  
Location Tracking ◽  
Main Trial ◽  
Phone Calls ◽  
Effective Manner ◽  
Research Platform

Abstract Background/Introduction TAILOR-PCI is the largest cardiovascular genotype-based randomized trial (NCT#01742117) investigating whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes after percutaneous coronary intervention (PCI). The TAILOR-PCI Digital Sub-Study tests the feasibility of extending original follow-up of 1 year to 2 years using state-of-the-art digital solutions. Deep phenotyping acquired during a clinical trial can be leveraged by extending follow-up in an efficient and cost-effective manner using digital technology. Purpose Our objective is to describe onboarding and engagement of participants initially recruited in a large, pragmatic, international, multi-center clinical trial to a digital registry. Methods TAILOR-PCI participants, within 23 months of their index PCI, were invited by letters containing a URL to the Digital Sub-Study website (http://tailorpci.eurekaplatform.org). These invitations were followed by phone calls, if no response to the letter, to determine reason for non-participation. A NIH-funded direct-to-participant digital research platform (the Eureka Research Platform) was used to onboard, consent and enroll participants for the digital follow-up. Participants were asked to answer health-related surveys at fixed intervals using the Eureka mobile app and desktop platform. To capture hospitalizations, participants could enable geofencing to allow background location tracking, which triggered surveys if a hospitalization was detected. Result(s) Letters were mailed to 893 of 929 eligible participants across 22 sites in the United States and Canada leading to 226 homepage visits and 118 registrations. There were 107 consents (12.0% of invited; mean age: 66.4±9.0; 19 females [18%]): 47 (44%) participants consented after the letter, 36 (34%) consented after the 1st call and 24 (22%) consented after a 2nd call. Among those who consented, 100 were eligible (7 did not have a smartphone) 81 downloaded the study mobile app and 73 agreed for geofencing (Figure 1). Among the 722 invited participants who were surveyed, 354 declined participation: due to lack of time (146; 20.2%), lack of smartphone (125; 17.3%), difficulty understanding (41; 5.7%), concern about using smartphone (34; 4.7%), concern of data privacy (14; 1.9%), concerns of location tracking (6; 0.8%) and other reasons (57; 7.9%). Conclusion Extended follow-up of a clinical trial using a digital platform is feasible but uptake in this study population was limited largely due to lack of time or a smartphone among participants. Based on data from other digital studies, uptake may also have been limited since digital follow-up consent was not incorporated at the time of consent for the main trial. Figure 1. Onboarding of the digital substudy Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

Implementing Digital Technology to Transitioning a Clinical Trial to a Registry – TAILOR-PCI Digital Study: Methods/Study Design (Preprint)

2021 ◽  
Author(s):  
Robert Avram ◽  
Derek So ◽  
Erin Iturriaga ◽  
Julia Byrne ◽  
Ryan Lennon ◽  
...  
Keyword(s):  
Clinical Trial ◽  
The United States ◽  
Completion Rate ◽  
Phone Call ◽  
Consent Rate ◽  
Digital Platform ◽  
Phone Calls ◽  
Patient Reported ◽  
Research Platform

BACKGROUND TAILOR-PCI was the largest cardiovascular genotype-based randomized clinical trial (RCT) investigating whether CYP2C19 genotype-guided selection of oral P2Y12 inhibitor therapy improved ischemic outcomes after percutaneous coronary intervention (PCI). The TAILOR-PCI Digital Registry was a novel proof-of-concept study that evaluated the feasibility of extending the main RCT follow-up period using a remote digital platform. OBJECTIVE To describe patients onboarding, engagement and results of a digital registry after enrollment in a RCT. METHODS In this intervention study, previously enrolled TAILOR-PCI patients in the United States and Canada within 24 months of randomization were invited by letters containing a URL to the TAILOR-PCI Digital Registry website (http://tailorpci.eurekaplatform.org), instructing them to download the study app. Patients previously enrolled in the TAILOR-PCI study, with a smartphone, were eligible to join the Digital Registry. Those who did not respond to the letter were contacted by phone to survey reasons for non-participation and were invited again to join the study. A direct-to-patient digital research platform (the Eureka Research Platform) was used to onboard, consent and enrol patients in the Digital Registry. Patients were asked to complete health-related surveys and provide follow-up data digitally. Consent rate to the Digital Registry, duration of participation in the Digital Registry and monthly activity completion rate. The hypothesis being tested was formulated before data collection began. RESULTS After the parent trial was completed, letters were mailed to 907 eligible patients (representing 19% of total enrolled in the RCT) across 24 sites, who were within 15.6 ± 5.2 months after randomization leading to 290 unique individuals visits to the Digital Registry website. Among those invited, 110 patients (12%) consented: 45 (41%) after the letter, 37 (34%) after the 1st phone call and 28 (25%) after a 2nd call. Of the 862 who didn’t consent after the letter, 453 patients (53%) did not respond to repeated phone calls and among the 409 patients who responded, 171 (41%) declined participation stating lack of time, 128 (31%), due to lack of smartphone and 47 (11%) due to difficulty understanding what was expected of them in the study. Patients who consented were older, had less diabetes or tobacco use; a greater proportion had bachelor's degrees or higher and were more computer literate than those who did not consent. The average completion rate of the 920 available monthly electronic visits was 64.9±7.6% without a decrease in this rate throughout the study duration. There were no differences between randomization arms in any patient reported outcomes using the digital platform. CONCLUSIONS Extended follow-up after enrollment in a RCT using a digital registry is technically feasible but was limited due to inability to contact most eligible patients, lack of time or access to a smartphone. Among those enrolled, most patients completed required electronic visits. Enhanced recruitment methods, such as introduction of the digital study at the time of RCT consent, provision of smartphone and robust study support for onboarding, should be explored further. CLINICALTRIAL TAILOR-PCI (Clinicaltrials.gov: NCT01742117)

Nurse Navigators telephone and web application follow-up intervention for patients treated with oral anticancer medication: an optimization of oncologists' medical time.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6544-6544
Author(s):  
Marie Ferrua ◽  
FATIMA YATIM ◽  
Aude Fourcade ◽  
Marilène Guillet Lacaze ◽  
Olivier Mir ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Web Application ◽  
Care Pathway ◽  
Mobile App ◽  
Biological Assessment ◽  
Oncological Treatment ◽  
Phone Calls ◽  
Anti Cancer ◽  
Medical Documents

6544 Background: Many interventions to improve safety and quality of oral anti-cancer medication have occurred the past few years. Frequently, these systems involve Nurse Navigators (NN) but rather limited data is actually available describing their activities and quantifying which intervention could have been performed without an oncologist's expertise. This is a major issue in optimizing the workload of oncologists statewide. Methods: The study was conducted at Gustave Roussy (Villejuif, France) as part of an assessment program of an intervention combining NN and mobile app dedicated to patients receiving oral cancer medication (cytotoxic, targeted therapies). A coding grid was developed to classify the NNs' activities from the intervention reports. NN interventions consist in regular follow-up calls and requests from patients and their relatives (via phone calls or mobile app). NN interventions recorded over a 24-month period were all encoded by two researchers. Results: 2395 interventions were analyzed concerning 236 patients, 1880 of which were regular follow-ups, and 515 patient requests. The majority of contacts were carried by phone conversation (94%). 52% of the interventions were followed-up upon by at least one additional action by the NN (n = 1250). In 25% (n = 318) of the interventions, the oncologist's expertise was required mainly because of the presence or aggravation of symptoms and/or toxicities or concerning oncological treatment (therapeutic protocol, biological assessment). 75% (n = 932) of the interventions have been processed successfully by NN by themselves. The principal actions carried out by the NN were: A. Contact or provide referral to a health professional or institution 24%, B. Advice to the patient 43%, C. Management of medical documents and appointments 6%; D. Administrative management 2%. Conclusions: Patients' needs for oral cancer drugs are mainly related to advice, information and coordination of the care pathway. In the majority of interventions, the NNs were able to manage these situations by themselves, which could optimize the workload of oncologists.

Abstract 201: Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad-necked, Bifurcation Aneurysms

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Alex M Spiotta
Keyword(s):  
United States ◽  
Clinical Trial ◽  
The United States ◽  
San Jose ◽  
Neck Size ◽  
Aneurysm Embolization ◽  
Wide Neck ◽  
The U.S

Background: The safety and probable benefit of the PulseRider ® (Pulsar Vascular, San Jose, CA) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, non-randomized, single arm clinical trial - the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction Trial (ANSWER). Objective: We present the results of the United States cases employing the PulseRider ® device as part of the ANSWER clinical trial. Methods: Aneurysms treated with the PulseRider ® device among U.S. sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study. Results: 34 patients were enrolled (29 female and 5 male) with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range 2.3 - 11.6 mm). In all patients the device was delivered and deployed. Immediate Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at six month follow up. A modified Rankin Score of 2 or less was seen in 94% of patients at 6 months. Conclusions: The results from the U.S. cases of the ANSWER trial demonstrate that the Pulse Rider® device is safe and effective as for the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist.

scholarly journals Cardiosphere-derived exosomal microRNAs for cardiac repair in pediatric dilated cardiomyopathy: preclinical and safety lead-in phase 1 clinical studies

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Hirai ◽  
K Baba ◽  
S Ohtsuki ◽  
H Oh
Keyword(s):  
Clinical Trial ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Myocardial Fibrosis ◽  
Cardiac Repair ◽  
Secondary Outcome ◽  
Swine Model ◽  
Funding Source ◽  
To Receive

Abstract Introduction Stem cell therapies have been shown to improve cardiac function; however, therapeutic potential of cardiosphere-derived cells (CDCs) in dilated cardiomyopathy (DCM) and the underlying mechanisms of paracrine effectors include CDC-secreted exosomes (CDCex) mediating cardiac repair remain unknown. Purpose- We aimed to evaluate the safety and therapeutic efficacy of CDCs in swine model of DCM and translate the preclinical results into children with DCM. Methods As a preclinical study, female Yorkshire pigs (n=15) were treated by intracoronary administration of microspheres (1.0×104 particles) to develop diffuse cardiac dysfunction and animals were randomly assigned to receive placebo or 9.0×106 CDC injection pretreated by DMSO or exosome inhibitor (EI; GW4869). CDCex-derived microRNAs (miRs) profile was assessed and ventricular ejection fraction (EF) was evaluated before and 1 month after cell infusion. In safety lead-in clinical trial, 5 patients with DCM (<18 years) with reduced EF (<40%) were prospectively enrolled to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function over 12 months. Results Compared with placebo control, DMSO-treated CDC infusion resulted in improved cardiac function with decrease in myocardial fibrosis (18.2±4.1% versus; 9.5±3.6%; P<0.001) and enhanced cardiomyocyte cycling (Ki67: 27.2±3.6/106 myocytes versus 43.9±6.0/106 myocytes; P=0.002) and neovascularization (von Willebrand factor: 644.8±84.3/mm2 versus 820.7±159.7/mm2; P=0.01) at 1 month. miR expression analysis showed that CDCex were highly enriched with miR-126, miR-132, miR-146a, miR-181b, miR-210, and miR-451. Inhibition of CDCex-derived miRs production by EI pretreatment did not affect CDC viability but rendered CDC ineffective in functional improvement (ΔEF: +5.4%±2.0% versus −1.0%±2.1%; P=0.002). One-year follow-up of clinical trial was completed in 5 patients with favorable profile and preliminary efficacy outcomes. Echocardiographic measurements revealed that CDC infusion increased EF from baseline to 12 months of follow up (28.5±10.7% versus 33.0±11.1%; P=0.038) in accordance with reduced native T1 mapping (1041.6±60.4 ms versus 984.8±39.3 ms; P=0.025). CDCex-derived miRs profiles from patients demonstrated that several miRs were exclusively enriched in CDCs but human cardiac fibroblasts included miR-126, miR-132, miR-146a, miR-181b, and miR-210. Notably, miR-146a expression levels were positively correlated with the reduction in myocardial fibrosis 12 months after CDC infusion (Δnative T1: r=0.896, P=0.040). Conclusions Intracoronary delivery of CDCs is safe and improves cardiac function through CDCex-derived miRs secretion in swine model of DCM. The safety lead-in results in patients warrant further assessment of clinical benefits and highlight miR-146a as a major paracrine mediator of CDC's antifibrotic function for clinical therapeutics. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Project for Practical Application of Regenerative Medicine (16bk0104052h0001, 17bk0104052h0002, 18bk0104052h0003) by the Japan Agency for Medical Research and Development

scholarly journals COVID-19 Follow-App. Mobile App-Based Monitoring of COVID-19 Patients after Hospital Discharge: A Single-Center, Open-Label, Randomized Clinical Trial

2022 ◽  
Vol 12 (1) ◽  
pp. 24
Author(s):  
Ester Marquez-Algaba ◽  
Marc Sanchez ◽  
Maria Baladas ◽  
Claudia España ◽  
Hermes Salvatore Dallo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Emergency Department ◽  
Hospital Discharge ◽  
Mobile App ◽  
Control Group ◽  
Primary Care Center ◽  
Open Label ◽  
Return Visits ◽  
Experimental Group

Introduction: In the midst of a pandemic, apps can be used to provide close follow-up, ensure that patients are monitored at home, avoid excessive pressure on medical facilities, prevent the movement of people (both patients and health professionals), and reduce the risk of infection. Objective: To adapt and validate the use of a smartphone application for outpatient follow-up of COVID-19 patients after hospital discharge. Methods: We conducted an open-label clinical trial at Hospital Universitari Vall d’Hebron in Barcelona, Spain. Patients were randomly assigned in a 1:1 ratio to be followed by the Farmalarm app or by their primary care center. The primary endpoint was the reduction in the need for in-person return visits. Results: From 31 March to 4 May 2020, 150 patients were enrolled in the study at hospital discharge: 74 patients were randomized to the experimental group, and 76 to the control group. All patients in the control group and all except for six in the experimental group completed the study. During hospitalization, before study inclusion, all but 4 (97.3%) had viral pneumonia, 91 (60.7%) required supplemental oxygen, and 16 (10.7%) required intensive care unit (ICU) admission. COVID-19–related return visits to the emergency department were significantly higher in the control group (7.9% vs. 0%; p = 0.028) in the per-protocol analysis. Telephone consultations with the emergency department were performed by 12 (15.8%) patients in the control group and 0 (0%) in the experimental group (p < 0.001). Satisfaction with outpatient monitoring was rated higher by the experimental group (5 vs. 4 points; p < 0.001). Conclusions: Following COVID-19 hospital discharge, home follow-up via a mobile app was effective in reducing in-person return visits without undermining patient satisfaction or perception of health, compared with standard follow-up.

scholarly journals NAITRE study on the impact of conditional cash transfer on poor pregnancy outcomes in underprivileged women: protocol for a nationwide pragmatic cluster-randomised superiority clinical trial in France

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e017321
Author(s):  
Marc Bardou ◽  
Bruno Crépon ◽  
Anne-Claire Bertaux ◽  
Aurélie Godard-Marceaux ◽  
Astrid Eckman-Lacroix ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prenatal Care ◽  
Primary Endpoint ◽  
Pregnancy Outcomes ◽  
Financial Incentives ◽  
High Income ◽  
Main Trial ◽  
Cluster Randomised ◽  
The Impact

IntroductionPrenatal care is recommended during pregnancy to improve neonatal and maternal outcomes. Women of lower socioeconomic status (SES) are less compliant to recommended prenatal care and suffer a higher risk of adverse perinatal outcomes. Several attempts to encourage optimal pregnancy follow-up have shown controversial results, particularly in high-income countries. Few studies have assessed financial incentives to encourage prenatal care, and none reported materno-fetal events as the primary outcome. Our study aims to determine whether financial incentives could improve pregnancy outcomes in women with low SES in a high-income country.Methods and analysisThis pragmatic cluster-randomised clinical trial includes pregnant women with the following criteria: (1) age above 18 years, (2) first pregnancy visit before 26 weeks of gestation and (3) belonging to a socioeconomically disadvantaged group. The intervention consists in offering financial incentives conditional on attending scheduled pregnancy follow-up consultations. Clusters are 2-month periods with random turnover across centres. A composite outcome of maternal and neonatal morbidity and mortality is the primary endpoint. Secondary endpoints include maternal or neonatal outcomes assessed separately, qualitative assessment of the perception of the intervention and cost-effectiveness analysis for which children will be followed to the end of their first year through the French health insurance database. The study started in June 2016, and based on an expected decrease in the primary endpoint from 18% to 14% in the intervention group, we plan to include 2000 women in each group.Ethics and disseminationEthics approval was first gained on 28 September 2014. An independent data security and monitoring committee has been established. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT02402855; pre-results.

scholarly journals Telehealth-Based Services During the COVID-19 Pandemic: A Systematic Review of Features and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Farnaz Khoshrounejad ◽  
Mahsa Hamednia ◽  
Ameneh Mehrjerd ◽  
Shima Pichaghsaz ◽  
Hossein Jamalirad ◽  
...  
Keyword(s):  
Technology Acceptance ◽  
Mixed Reality ◽  
Healthcare Providers ◽  
Healthcare Services ◽  
The United States ◽  
Text Messages ◽  
Synchronous Communication ◽  
Function Type ◽  
Phone Calls

Background: As an ever-growing popular service, telehealth catered for better access to high-quality healthcare services. It is more valuable and cost-effective, particularly in the middle of the current COVID-19 pandemic. Accordingly, this study aimed to systematically review the features and challenges of telehealth-based services developed to support COVID-19 patients and healthcare providers.Methods: A comprehensive search was done for the English language and peer-reviewed articles published until November 2020 using PubMed and Scopus electronic databases. In this review paper, only studies focusing on the telehealth-based service to support COVID-19 patients and healthcare providers were included. The first author's name, publication year, country of the research, study objectives, outcomes, function type including screening, triage, prevention, diagnosis, treatment or follow-up, target population, media, communication type, guideline-based design, main findings, and challenges were extracted, classified, and tabulated.Results: Of the 5,005 studies identified initially, 64 met the eligibility criteria. The studies came from 18 countries. Most of them were conducted in the United States and China. Phone calls, mobile applications, videoconferencing or video calls, emails, websites, text messages, mixed-reality, and teleradiology software were used as the media for communication. The majority of studies used a synchronous communication. The articles addressed the prevention, screening, triage, diagnosis, treatment, and follow-up aspects of COVID-19 which the most common purpose was the patients' follow-up (34/64, 53%). Thirteen group barriers were identified in the literature, which technology acceptance and user adoption, concerns about the adequacy and accuracy of subjective patient assessment, and technical issues were the most frequent ones.Conclusion: This review revealed the usefulness of telehealth-based services during the COVID-19 outbreak and beyond. The features and challenges identified through the literature can be helpful for a better understanding of current telehealth approaches and pointed out the need for clear guidelines, scientific evidence, and innovative policies to implement successful telehealth projects.

Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad-Necked, Bifurcation Aneurysms

Neurosurgery ◽  
2017 ◽  
Vol 81 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Alejandro M. Spiotta ◽  
Colin P. Derdeyn ◽  
Satoshi Tateshima ◽  
Jay Mocco ◽  
R. Webster Crowley ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trial ◽  
The United States ◽  
Neck Size ◽  
Aneurysm Embolization ◽  
Wide Neck

Abstract BACKGROUND: The safety and probable benefit of the PulseRider (Pulsar Vascular, Los Gatos, California) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, nonrandomized, single arm clinical trial—the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction (ANSWER) Trial. OBJECTIVE: To present the results of the United States cases employing the PulseRider device as part of the ANSWER clinical trial. METHODS: Aneurysms treated with the PulseRider device among sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study. RESULTS: Thirty-four patients were enrolled (29 female and 5 male) with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range 2.3-11.6 mm). In all patients, the device was delivered and deployed. Immediate Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at 6-month follow-up. A modified Rankin Score of 2 or less was seen in 94% of patients at 6 months. CONCLUSION: The results from the ANSWER trial demonstrate that the PulseRider device is safe and offers probable benefit as for the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist.

Endovascular embolization of 150 basilar tip aneurysms with Guglielmi detachable coils: results of the Food and Drug Administration multicenter clinical trial

1998 ◽  
Vol 5 (4) ◽  
pp. E3 ◽  
Author(s):  
Joseph M. Eskridge ◽  
Joon K. Song ◽  
_ _
Keyword(s):  
Clinical Trial ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
The United States ◽  
Guglielmi Detachable Coils ◽  
Unruptured Aneurysms ◽  
Ruptured Aneurysms ◽  
Platinum Coil ◽  
Detachable Coils

To assess the safety and efficacy of aneurysm embolization performed using Guglielmi detachable coils (GDCs), the authors reviewed the results of a cohort of 150 patients with either ruptured (83 patients) or unruptured (67 patients) basilar tip aneurysms treated with these detachable platinum coil devices in the early part of the United States multicenter GDC clinical trial that led to Food and Drug Administration approval for the device. The most common presentation in this cohort of patients was headache (53%). All patients were entered into the trial after neurosurgical assessment excluded them as candidates for surgical clipping of their aneurysms. Greater than 90% coil packing was achieved in 75% of the patients. For those patients in whom follow-up information was available, the mean angiographic and clinical evaluation follow-up time for 61 patients with ruptured aneurysms was 13.7 months (range 0-43 months) and that for the 49 patients with unruptured aneurysms was 9.8 (range 0-40 months). Conservative mortality rates included up to 23% for the ruptured aneurysm group and up to 12% for the unruptured aneurysm group; the rebleeding rate for treated ruptured aneurysms was up to 3.3% and the bleeding rate for unruptured aneurysms up to 4.1%. Permanent deficits due to stroke in patients with ruptured or unruptured aneurysms occurred in up to 5% and 9%, respectively. Vasospasm occurred in 8% of the patients; it was associated with two deaths. Periprocedural mortality was 2.7% (four patients with ruptured aneurysms). Detachable platinum coil embolization is a promising treatment for ruptured basilar tip aneurysms that are not surgically clippable; in selected patients it offers lower incidences of morbidity and mortality compared with conservative medical management. The role of this procedure in unruptured basilar tip aneurysms is unclear with less supportive results. More long-term follow-up evaluation is necessary and results are expected to improve.

scholarly journals Ibrutinib Maintenance after Chemoimmunotherapy Is Feasible and Results in Excellent Progression-Free and Overall Survival in Patients with Detectable MRD after Chemoimmunotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1764-1764
Author(s):  
Nayara Ribeiro Guedes ◽  
Ana Rita Da Fonseca ◽  
Thiago Xavier Carneiro ◽  
Vinicius Campos de Molla ◽  
Rodrigo Santucci Silva ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Peripheral Blood ◽  
The United States ◽  
Clinical Indication ◽  
First Line ◽  
One Year

Introduction Given the variety of highly effective therapies available for chronic lymphocytic leukemia (CLL), a tailored treatment strategy is needed. Fixed-duration chemoimmunotherapy can produce sustained and deep responses. The presence of minimal residual disease (MRD) has been studied as an independent prognostic factor for long-term survival in patients with CLL. Multiple novel agents have been recently approved for previously untreated patients, including the BTK inhibitor, ibrutinib, but its effect on MRD is still unclear. We performed a prospective clinical trial to evaluate the efficacy of maintenance therapy with ibrutinib in patients with detectable MRD after first-line chemoimmunotherapy. Patients and methods In this phase 2 clinical trial, we assessed the efficacy and safety of ibrutinib 420 mg daily as maintenance therapy, until progression or unacceptable toxicity, after achieving complete remission (CR) or partial remission (PR) with chemoimmunotherapy in previously untreated 40 patients with CLL from 9 centers in Brazil. The median age was 60 years (range: 43-85 years). Twenty-nine patients (73%) had been treated with fludarabine and cyclophosphamide (FC) ± rituximab, 10 (25%) with chlorambucil ± rituximab, and one (2%) with bendamustine + rituximab. Responses definitions were based on the 2018 iwCLL guidelines. Twenty-five patients (63%) were in CR and 15 (37%) in PR before the start of maintenance. Patients with detectable MRD within 12 months after the end of the first line chemoimmunotherapy were included. Besides, three patients with undetectable MRD were also included in order to evaluate possible effects of ibrutinib on that group. Responses were assessed monthly during the first year and every three months thereafter. MRD was assessed by 8-color flow cytometry in the bone marrow and in the peripheral blood before and after one year of maintenance therapy, and in peripheral blood every 3 months thereafter. Primary end point was progression-free survival (PFS). Results Median follow-up time was 25 months (range: 12-46 months). Among the 40 patients included, two patients withdrew consent (one just after inclusion and one after 30 days), and one patient died 7 days after ibrutinib was started due to an unrelated cause (ruptured aortic aneurysm). Thirty-seven patients were treated with ibrutinib and prospectively followed. The median PFS and overall survival (OS) were not reached. PFS and OS at 2 years were 92% and 95%, respectively. Among the 15 patients who started maintenance in PR, 8 (53%) achieved CR (3 of which had incomplete hematologic recovery), and 7 had complete nodal response, but remained in PR due to persistent lymphocytosis. Among the 22 who entered maintenance in CR, all but one remained in CR: 1 patient presented ≥ 50% increase in his baseline lymphocyte count 40 months after maintenance was started, but remains on ibrutinib with no cytopenias or clinical indication to treatment change. Among the 34 patients who had detectable MRD, 9% had at least 1-log reduction after one year and 20% after 2 years. Besides, one patient achieved undetectable MRD so far, 30 months after ibrutinib was started. All 3 patients with undetectable MRD at baseline, remained undetectable. Sustained increases from baseline values in the hemoglobin and platelet levels were observed in 30 patients (81%). Adverse events of any grade that occurred during maintenance with ibrutinib included diarrhea (23%), nausea (10%), and fatigue (8%), but only 2 patients had grade 3 diarrhea, associated with the concomitant use of metformin that resolved after discontinuation. Atrial fibrillation occurred intermittently in 3 patients during maintenance. A total of 81% of patients remain on ibrutinib. Four patients discontinued the drug: one after 8 months to perform a stem cell transplant by the decision of the treating physician, one after 10 months due to adverse events (lymphomatoid granulomatosis), and 2 after 13 months due to logistic difficulties to remain on regular follow up. Conclusions Maintenance with ibrutinib for CLL patients achieving CR or PR after chemoimmunotherapy resulted in excellent PFS and OS, and sustained improvement in hematologic variables irrespectively of achieving undetectable MRD. Efficacy of this regimen compares well to other frontline chemo-free treatments offered to patients with CLL in the United States and Europe. Disclosures No relevant conflicts of interest to declare.

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