LitCovid-sentences  

PubMed:32560744 JSONTXT 20 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-13 Sentence denotes AGILE-ACCORD:
T2 14-196 Sentence denotes A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19:
T3 197-270 Sentence denotes A structured summary of a study protocol for a randomised platform trial.
T4 271-282 Sentence denotes OBJECTIVES:
T5 283-398 Sentence denotes Phase I - To determine the optimal dose of each candidate (or combination of candidates) entered into the platform.
T6 399-629 Sentence denotes Phase II - To determine the efficacy and safety of each candidate entered into the platform, compared to the current Standard of Care (SoC), and recommend whether it should be evaluated further in a later phase II & III platforms.
T7 630-897 Sentence denotes TRIAL DESIGN: AGILE-ACCORD is a Bayesian multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19.
T8 898-1240 Sentence denotes Designed as a master protocol with each candidate being evaluated within its own sub-protocol (Candidate Specific Trial (CST) protocol), randomising between candidate and SoC with 2:1 allocation in favour of the candidate (N.B the first candidate has gone through regulatory approval and is expected to open to recruitment early summer 2020).
T9 1241-1317 Sentence denotes Each dose will be assessed for safety sequentially in cohorts of 6 patients.
T10 1318-1428 Sentence denotes Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort.
T11 1429-1442 Sentence denotes PARTICIPANTS:
T12 1443-1661 Sentence denotes Patient populations can vary between CSTs, but the main eligibility criteria include adult patients (≥18 years) who have laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
T13 1662-1736 Sentence denotes We will include both severe and mild-moderate patients defined as follows:
T14 1737-2242 Sentence denotes Group A (severe disease) - patients with WHO Working Group on the Clinical Characteristics of COVID-19 infection 9-point ordinal scale of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, non-invasive ventilation or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (hospitalised, ventilation and additional organ support); Group B (mild-moderate disease) - ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO2) >94% RA.
T15 2243-2395 Sentence denotes If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible.
T16 2396-2475 Sentence denotes Participants will be recruited from England, North Ireland, Wales and Scotland.
T17 2476-2504 Sentence denotes INTERVENTION AND COMPARATOR:
T18 2505-2581 Sentence denotes Comparator is the current standard of care (SoC), in some CSTs plus placebo.
T19 2582-2781 Sentence denotes Candidates that prevent uncontrolled cytokine release, prevention of viral replication, and other anti-viral treatment strategies are at various stages of development for inclusion into AGILE-ACCORD.
T20 2782-2817 Sentence denotes Other CSTs will be added over time.
T21 2818-2999 Sentence denotes There is not a set limit on the number of CSTs we can include within the AGILE-ACCORD Master protocol and we will upload each CST into this publication as each opens to recruitment.
T22 3000-3014 Sentence denotes MAIN OUTCOMES:
T23 3015-3023 Sentence denotes Phase I:
T24 3024-3129 Sentence denotes Dose limiting toxicities using Common Terminology Criteria for Adverse Events v5 Grade ≥3 adverse events.
T25 3130-3139 Sentence denotes Phase II:
T26 3140-3235 Sentence denotes Agreed on a CST basis depending on mechanism of action of the candidate and patient population.
T27 3236-3556 Sentence denotes But may include; time to clinical improvement of at least 2 points on the WHO 9-point category ordinal scale [measured up to 29 days from randomisation], progression of disease (oxygen saturation (SaO2) <92%) or hospitalization or death, or change in time-weighted viral load [measured up to 29 days from randomisation].
T28 3557-3571 Sentence denotes RANDOMISATION:
T29 3572-3676 Sentence denotes Varies with CST, but default is 2:1 allocation in favour of the candidate to maximise early safety data.
T30 3677-3696 Sentence denotes BLINDING (MASKING):
T31 3697-3802 Sentence denotes For the safety phase open-label although for some CSTs may include placebo or SoC for the efficacy phase.
T32 3803-3842 Sentence denotes NUMBERS TO BE RANDOMISED (SAMPLE SIZE):
T33 3843-3863 Sentence denotes Varies between CSTs.
T34 3864-4228 Sentence denotes However simulations have shown that around 16 participants are necessary to determine futility or promise of a candidate at a given dose (in efficacy evaluation alone) and between 32 and 40 participants are required across the dose-finding and efficacy evaluation when capping the maximum number of participants contributing to the evaluation of a treatment at 40.
T35 4229-4242 Sentence denotes TRIAL STATUS:
T36 4243-4522 Sentence denotes Master protocol version number v5 07 May 2020, trial is in setup with full regulatory approval and utilises several digital technology solutions, including Medidata's Rave EDC [electronic data capture], RTSM for randomisation and patient eConsent on iPads via Rave Patient Cloud.
T37 4523-4632 Sentence denotes The recruitment dates will vary between CSTs but at the time of writing no CSTs are yet open for recruitment.
T38 4633-4652 Sentence denotes TRIAL REGISTRATION:
T39 4653-4706 Sentence denotes EudraCT 2020-001860-27 14th March 2020 FULL PROTOCOL:
T40 4707-4815 Sentence denotes The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).
T41 4816-4996 Sentence denotes In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.