The occurrence of grade 4 adverse events and survival outcomes in patients with nonsquamous non-small cell lung cancer receiving bevacizumab with chemotherapy in the phase III PointBreak and AVAiL studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19022-e19022
Author(s):  
Liza Cosca Villaruz ◽  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Larry Leon ◽  
Sebastien Hazard ◽  
...  
Keyword(s):  
Cox Model ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

e19022 Background: Progression-free survival (PFS) is a key trial end point for clinical practice, as it relates to a change of treatment line. Grade 4 progression-free survival (G4PFS; defined as time from treatment start to the earlier of progressive disease [PD], onset of a G4 adverse event [AE], or death from any cause) is a composite end point incorporating a measure of tolerability to PFS. This post hoc analysis evaluates G4PFS and the effect of G4 AEs on PFS and overall survival (OS) in patients (pts) enrolled in PointBreak (PB) and AVAiL. Methods: Pts in PB were randomized to bevacizumab (BEV) 15 mg/kg q3w with carboplatin and paclitaxel (CP) or pemetrexed (CPem) for ≤4 cycles. Eligible pts received either BEV or BEV + Pem q3w until PD or unacceptable toxicity. Pts in AVAiL received cisplatin and gemcitabine for ≤6 cycles and either placebo or BEV (7.5 or 15 mg/kg) q3w until PD. AEs were graded via NCI-CTCAE v3.0. Kaplan-Meier and Cox model methods were used to estimate medians and hazard ratios (HRs) for PFS, G4PFS, and OS. PFS and OS were also compared in each arm for pts with occurrence of a G4 AE before week 12 of treatment vs those without. Results: Of those receiving BEV, ~30% of AVAiL pts and 38% of PB pts had a G4 AE. Uncomplicated neutropenia was the most common G4 AE in the CP + BEV arm of PB (26%) and in the BEV arms of AVAiL (11%). PFS, G4PFS, and outcomes by G4 AE occurrence are shown (Table). Conclusions: In both the PB and AVAiL trials, median G4PFS was numerically shorter than median PFS. G4 AE occurrence, however, did not affect subsequent PFS or OS in either trial. Clinical trial information: NCT00762034 and NCT00806923. [Table: see text]

Magnitude of progression-free survival (PFS) improvement and treatment (Tx) duration in metastatic colorectal cancer (mCRC) for bevacizumab (BV) in combination with oxaliplatin-containing regimens: An analysis of two phase III studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
B. J. Giantonio ◽  
N. J. Meropol ◽  
P. J. Catalano ◽  
V. Ng ◽  
R. Oliver ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Two Phase ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Phase Iii Studies

4073 Background: In trials of BV with FOLFOX (fluorouracil, leucovorin, oxaliplatin) for mCRC, variability in the magnitude of PFS improvement has been reported [HR=0.61 in E3200 vs HR= 0.83 (FOLFOX or CAPOX (capecitabine and oxaliplatin)) in NO16966]. We propose that differences in rates of treatment discontinuation (D/C) for adverse events (AE) between these studies may have resulted in differences in the observed benefits associated with BV. We explored Tx duration (proportion of patients on Tx) and Tx D/C data at median PFS for the BV containing arms of each study. Methods: ECOG study E3200 randomized previously treated patients with mCRC to FOLFOX ± BV (10 mg/kg). NO16966 employed a 2x2 design that randomized previously untreated patients with mCRC to CAPOX vs FOLFOX and to BV (5 mg/kg) or placebo. In both trials, study Tx was defined as any component of the prescribed regimen. PFS was estimated from Kaplan-Meier curves, and hazard ratios (HR) for PFS were estimated by Cox regression. Results: Median PFS for the BV containing arm of the study: 30 weeks for E3200; 42 weeks for NO16966 Conclusion: These data suggest possible differences between the two studies in Tx duration and Tx D/C patterns with a greater proportion of patients on NO16966 discontinuing Tx for any AE. Duration of study Tx might have affected both the incidence of AEs and the magnitude of PFS benefit observed for the addition of bevacizumab to oxaliplatin-based chemotherapy in these studies. Attention to Tx duration and Non-PD Tx D/C in future clinical trials will be important when considering PFS as a primary efficacy endpoint. [Table: see text] No significant financial relationships to disclose.

Final overall survival (OS) analysis with modeling of crossover impact in the phase III GRID trial of regorafenib vs placebo in advanced gastrointestinal stromal tumors (GIST).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 156-156 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Failure Time ◽  
Cox Model ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Positive Trend ◽  
Structural Failure ◽  
Free Survival ◽  
Hazard Ratios ◽  
Background Grid ◽  
The Impact

156 Background: GRID showed that regorafenib (REG) improves progression-free survival (PFS; primary endpoint) vs placebo (PBO) in patients (pts) with advanced GIST after failure of at least imatinib and sunitinib (HR 0.27; 1-sided p < 0.0001). An interim OS analysis at the time of the primary PFS analysis showed a positive trend (HR 0.77; p = 0.199) despite 85% of PBO pts crossing over to REG. An exploratory analysis modeling the impact of crossover on OS suggested a benefit for REG. We present exploratory analyses of OS comparing crossover correction results at different times, including at the planned final OS analysis. Methods: Data cut-off dates for OS analyses were 26 Jan 2012 (final PFS analysis), 31 Jan 2014, and 8 Jun 2015 (final OS analysis). The impact of crossover on OS was modeled using 2 randomization-based methods: rank preserving structural failure time (RPSFT) and iterative parameter estimation (IPE), both considered best choice among correction analytics. Hazard ratios (HRs) and 95% CIs were derived using the Cox model. Results: Pts were randomized (2:1) to REG (n = 133) or PBO (n = 66). Data maturity in terms of deaths of randomized pts was 23%, 70%, and 81%. At data cut-off for the final OS analysis, a total of 162 deaths occurred: REG 109 (82%) and PBO 53 (80%); 7 pts remained on treatment. Compared to the 2012 OS analysis, continued crossover treatment further diluted the treatment effect, evidenced by the increasing HR in the ITT analysis at later times (Table). Conclusions: IPE correction provides more stable estimated median times and HRs than RPSFT. These exploratory analyses modeling the impact of crossover to active drug suggest that REG has a greater OS benefit than noted in the ITT analysis. Such sensitivity analytics are needed to understand fully the benefits of active drugs in crossover trials. Clinical trial information: NCT01271712. [Table: see text]

Adverse events (AEs) with maintenance olaparib in patients with a germline BRCA mutation (gBRCAm) and metastatic pancreatic cancer (mPaC): Phase III POLO trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 686-686
Author(s):  
Michele Reni ◽  
Hedy L. Kindler ◽  
Pascal Hammel ◽  
Eric Van Cutsem ◽  
Teresa Macarulla ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Brca Mutation ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Germline Brca Mutation ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

686 Background: In POLO (NCT02184195), maintenance olaparib was well tolerated and led to a significant progression-free survival benefit vs placebo in patients with a gBRCAm and mPaC whose disease had not progressed on first-line platinum-based chemotherapy (HR 0.53; 95% CI 0.35–0.82) (Golan et al. NEJM 2019). We analyzed common AEs and their management in POLO. Methods: Patients were randomized (3:2) to maintenance olaparib (tablets; 300 mg bid) or placebo until disease progression or unacceptable toxicity. AEs were graded using CTCAE v4.0. Results: Of 154 randomized patients, 151 were treated (olaparib, n=91; placebo, n=60) and included in safety analyses. Median treatment duration was 6.0 months (m) for olaparib and 3.7 m for placebo. Management of fatigue/asthenia, nausea, anemia and vomiting included supportive treatment and/or dose modification; few patients discontinued treatment due to AEs (Table). Of patients with anemia, 14 olaparib recipients received a blood transfusion while on study treatment; one olaparib recipient received epoetin beta. Conclusions: The AE profile of maintenance olaparib in patients with a gBRCAm and mPaC was consistent with that seen in other tumor types.Common AEs of fatigue/asthenia, nausea, anemia and vomiting occurred early, were manageable and led to few treatment discontinuations. Clinical trial information: NCT02184195 . [Table: see text]

Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5516-5516 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  
Keyword(s):  
Cox Model ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Testing Procedure ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Free Survival ◽  
End Point ◽  
Final Survival

5516 Background: SPARTAN evaluated APA vs PBO in pts with nmCRPC and a prostate-specific antigen doubling time of ≤ 10 mo receiving androgen deprivation therapy (ADT). At primary end point analysis of metastasis-free survival (MFS), APA significantly improved median MFS by 2 yrs, as well as time to metastasis, progression-free survival, and time to symptomatic progression vs PBO (Smith, et al. NEJM 2018); overall survival (OS) results were immature. SPARTAN was unblinded upon meeting the primary end point; pts still on PBO were allowed to cross over to APA. Final survival results are reported herein. Methods: 1207 nmCRPC pts were randomized 2:1 to APA (240 mg QD) or PBO plus ongoing ADT. At progression, pts could receive open-label sponsor-provided abiraterone acetate + prednisone. After the primary efficacy end point (MFS) was met, 76 PBO pts (19%) crossed over to APA. OS and time to cytotoxic chemotherapy (TTCx) were tested by group sequential testing procedure with O’Brien-Fleming (OBF)-type alpha spending function. Time-to-event end points were analyzed by Kaplan-Meier method and Cox model. A sensitivity analysis for OS, accounting for crossover using a naïve censoring approach, was conducted. Results: With follow-up of 52.0 mo, 428 (of 427 required) OS events had occurred. Median treatment duration: APA, 32.9 mo; PBO, 11.5 mo. Median OS was significantly longer with APA + ADT vs PBO + ADT (73.9 vs 59.9 mo), (hazard ratio [HR], 0.784, Table). APA significantly lengthened TTCx (HR, 0.629). Discontinuation rates (APA vs PBO) due to progressive disease were 42.7% vs 73.9%, and due to adverse events (AE) 15.2% vs 8.4%. Safety was consistent with previous reports; grade 3/4 treatment-emergent (TE) AEs of special interest were rash 5.2%, fractures 4.9%, falls 2.7%, ischemic heart disease 2.6%, hypothyroidism 0%, and seizures 0%. 1 TEAE leading to death (myocardial infarction) was considered potentially APA related. Conclusions: In pts with nmCRPC, APA + ADT significantly improved OS compared with PBO + ADT, with median OS > 6 yr in the APA + ADT group and 14 mo improvement over PBO + ADT. Benefit from APA was observed despite a 19% crossover from PBO. The safety profile of APA was consistent with prior interim analyses. Clinical trial information: NCT01946204 . [Table: see text]

An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9013-9013 ◽  
Author(s):  
Axel Hauschild ◽  
Jean Jacques Grob ◽  
Lev V. Demidov ◽  
Thomas Jouary ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Free Survival ◽  
Independent Review ◽  
Clinical Trial Information

9013 Background: Dabrafenib is a selective BRAF inhibitor with demonstrated efficacy in BRAF V600E-positive mutation in MM. The primary analysis of BREAK-3 (NCT01227889) compared progression-free survival (PFS) in patients (pts) with BRAF V600E-positive mutation MM treated with dabrafenib or DTIC. Methods: Median PFS for dabrafenib of 5.1 months (mo) and study methods were previously described (Hauschild A, et al. Lancet. 2012,380:358–365). Independent review ended at the primary analysis. PFS was updated in Jun 2012 at median follow-up of 10.5 mo for dabrafenib (67% of PFS events), and 9.9 mo for DTIC. Median overall survival (OS) was not reached, so another analysis of OS and safety was performed with data as of Dec 2012, at which time the median follow-up was 15.2 (dabrafenib) and 12.7 (DTIC) mo. PFS of subjects who crossed over was also evaluated at that time. Results: PFS hazard ratio was 0.37 [95% CI; 0.23, 0.57]; median PFS was 6.9 mo dabrafenib and 2.7 mo DTIC. In Dec 2012, 36/63 DTIC pts crossed over; median PFS was 4.3 [95% CI; 4.1, 6.1] mos. OS is presented in the Table.The four most common adverse events (AE) on the dabrafenib arm were hyperkeratosis (39%), headache (35%), arthralgia (35%), and pyrexia (32%). Serious AEs ≥ 5% on the dabrafenib arm included cutaneous squamous cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). Conclusions: Longer follow-up confirms the benefits of dabrafenib on PFS and response rate. Median OS in the dabrafenib arm was over 18 mo and over 15 mo in the DTIC arm. OS results are confounded by crossover of DTIC pts to dabrafenib and likely by subsequent therapy after progression. The effects of subsequent therapy results will be investigated. The safety profile had no significant changes. Clinical trial information: NCT01227889. [Table: see text]

Results of subset analyses on overall survival (OS) from study CA184-043: Ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Charles G. Drake ◽  
Eugene D. Kwon ◽  
Karim Fizazi ◽  
Alberto Bossi ◽  
Alfons JM van den Eertwegh ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Prognostic Features ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
To Receive ◽  
Clinical Trial Information

2 Background: The CA184-043 phase 3 study did not reach statistical significance for its primary endpoint of OS (HR=0.85, p=0.053). However, antitumor activity was observed in other efficacy endpoints, including progression-free survival. Prespecified subset analyses were performed to understand if any prognostic features may identify mCRPC patients (pts) more likely to benefit from Ipi treatment. Methods: 799 pts were randomized to receive a single dose of radiotherapy (RT) followed by either Ipi (N=399) or Pbo (N=400). Prespecified subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Prespecified subset analyses suggested that Ipi may be more active in pts with favorable prognostic factors, including no visceral disease, alkaline phosphatase <1.5 ULN, and hemoglobin ≥11 g/dL (Table). The safety profile in this study was consistent with previous reports of Ipi. Conclusions: Based on these subset analyses, Ipi added to RT appears to have greater activity than RT alone in pts with a favorable prognostic profile. These results support continued investigation of Ipi in the ongoing CA184-095 study in chemotherapy-naive mCRPC pts. Clinical trial information: NCT00861614. [Table: see text]

Onset of neutropenia as an indicator of treatment response in the phase 3 RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo in patients with metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 775-775 ◽  
Author(s):  
Atsushi Ohtsu ◽  
Takayuki Yoshino ◽  
Alfredo Falcone ◽  
Rocio Garcia-Carbonero ◽  
Guillem Argiles ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Free Survival ◽  
Initial Onset ◽  
Grade 3 ◽  
Post Hoc ◽  
First Time ◽  
Clinical Trial Information

775 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil. Primary results of the RECOURSE trial demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (pbo) in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies. Neutropenia is a common TAS-102–associated adverse event and it has been hypothesized to be associated with a relatively high FTD concentration in pts. Methods: RECOURSE data were analyzed post hoc for correlations between onset of neutropenia (Grade 3/4) and survival benefit. Results: Of 533 pts given TAS-102, 75 (14%) developed Grade 3/4 neutropenia in treatment cycle 1, 86 (16%) for the first time in cycle 2, and 39 (7%) for the first time in cycle ≥3. Onset of neutropenia at any cycle was associated with longer median OS and PFS compared with no neutropenia. A consistent survival benefit was observed regardless of the cycle of initial onset of neutropenia, as demonstrated by the hazard ratio (against cycle-matched pbo control groups) and corresponding median OS differences (Table). Conclusions: An association between occurrence of earliest onset of Grade 3/4 neutropenia and survival benefit was observed. The data indicate that such survival benefit occurred regardless of whether the initial onset of neutropenia occurred after cycle 1, cycle 2, or later. Further analyses are required to fully determine whether FTD pharmacokinetics correlate with TAS-102 efficacy and onset of neutropenia, and whether cycle initiation delays affect response. Clinical trial information: NCT01607957. [Table: see text]

Carfilzomib (K) in relapsed and refractory multiple myeloma (RRMM): Frailty subgroup analysis from phase III ASPIRE and ENDEAVOR.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8028-8028 ◽  
Author(s):  
Thierry Facon ◽  
Ruben Niesvizky ◽  
Katja Weisel ◽  
Sara Bringhen ◽  
P. Joy Ho ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Frailty Status ◽  
Improved Outcomes ◽  
Comorbidity Index ◽  
Post Hoc ◽  
Frailty Score

8028 Background: K-based regimens improved progression-free survival (PFS) and overall survival (OS) in RRMM patients (pts) in ASPIRE (K [27 mg/m2]-lenalidomide-dexamethasone [KRd] vs Rd) and ENDEAVOR (K [56 mg/m2]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), regardless of age. Frailty scores have been developed based on age, comorbidities, and functional status (Palumbo Blood 2015;125:2068–74; Facon Blood 2015;126:4239). We assessed post hoc pt outcomes by frailty status. Methods: PFS, OS, and safety were assessed by treatment arm and frailty score (based on age, medical history-derived Charlson Comorbidity Index, and ECOG performance status); frailty scores: 0 = fit, 1 = intermediate (int), and ≥2 = frail. Results: Pt frailty status was balanced between treatment arms in ASPIRE and ENDEAVOR. Median PFS and OS were longer with K-based regimens vs controls in ASPIRE and ENDEAVOR across frailty subgroups (Table). Rates of treatment-emergent adverse events are summarized in the Table. Conclusions: Kd56 and KRd consistently improved outcomes vs Vd and Rd, respectively, in all frailty subgroups as defined by the algorithm above. These findings support the favorable benefit-risk profile of KRd and Kd56 regardless of frailty score. Clinical trial information: NCT01080391 and NCT01568866. [Table: see text]

Project Switch: Docetaxel as a potential synthetic control in metastatic non-small cell lung cancer (mNSCLC) trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9105-9105 ◽  
Author(s):  
Michael E. Menefee ◽  
Yutao Gong ◽  
Pallavi Shruti Mishra-Kalyani ◽  
Rajeshwari Sridhara ◽  
Bindu Kanapuru ◽  
...  
Keyword(s):  
Randomized Trials ◽  
Progression Free Survival ◽  
Experimental Therapy ◽  
Synthetic Control ◽  
Small Cell Lung ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Real World Evidence ◽  
The Impact

9105 Background: Docetaxel is a common comparator arm to test novel therapies in post-platinum mNSCLC trials. The advent of Real World Evidence (RWE) has renewed interest in the use of synthetic control arms (control arms from previously conducted randomized trials) to improve accrual to trials and increase patient access of promising experimental agents. We reviewed legacy second-line (2L) mNSCLC trials to assess the impact of switching docetaxel control arms from one trial to another and compare to an experimental regimen. Methods: We identified 5 contemporary 2L trials that enrolled 2013 patients receiving an experimental therapy vs. docetaxel: 5 immunoncology head-to-head trials (one with 2 arms) and one anti-VEGF add-on trial. Kaplan-Meier curves of overall survival (OS) and progression-free survival (PFS) were produced for docetaxel controls. We calculated OS and PFS hazard ratios and 95% confidence intervals for each synthetic trial. A pooled doc arm was also compared with each experimental agent. Results: See Table. Conclusions: Both individual and pooled docetaxel switching of control arms approximated the original OS HR and 95% CI. Methods such as bootstrapped sampling and propensity score matching will be performed in an effort to more closely approximate the original trial characteristics. [Table: see text]

scholarly journals Brigatinib vs Alectinib in Crizotinib-Resistant Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer (ALTA-3)

2021 ◽  
Author(s):  
Sanjay Popat ◽  
Geoffrey Liu ◽  
Shun Lu ◽  
Gregory Song ◽  
Xin Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
End Point

Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK+ non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations. Head-to-head comparisons of next-generation ALK inhibitors in patients with ALK+ NSCLC progressing on crizotinib will contribute toward optimizing survival. This international, Phase III, randomized, open-label study (ALTA-3) will therefore assign patients with locally advanced or metastatic ALK+ NSCLC progressing on crizotinib to receive either brigatinib 180 mg qd (7-day lead-in at 90 mg qd) or alectinib 600 mg twice daily. The primary end point is progression-free survival as assessed by a blinded Independent Review Committee; the key secondary end point is overall survival. Trial registration number: NCT03596866  (ClinicalTrials.gov)

Sign in / Sign up

Export Citation Format

Share Document