LitCovid-sentences  

PubMed:32736597 JSONTXT 21 Projects

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Id Subject Object Predicate Lexical cue
T1 0-14 Sentence denotes PROTECT Trial:
T2 15-169 Sentence denotes A cluster-randomized study with hydroxychloroquine versus observational support for prevention or early-phase treatment of Coronavirus disease (COVID-19):
T3 170-245 Sentence denotes A structured summary of a study protocol for a randomized controlled trial.
T4 246-257 Sentence denotes OBJECTIVES:
T5 258-370 Sentence denotes Hydroxychloroquine has shown to have antiviral activity in vitro against coronaviruses, specifically SARS-CoV-2.
T6 371-513 Sentence denotes It is believed to block virus infection by increasing endosomal pH required for virus cell fusion and glycosylation of viral surface proteins.
T7 514-755 Sentence denotes In addition to its antiviral activity, hydroxychloroquine has an immune-modulating activity that may synergistically enhance its antiviral effect in vivo, making it a potentially promising drug for the prevention and the cure of SARS-CoV-19.
T8 756-896 Sentence denotes However, randomized controlled trials are needed to assess whether it can be used safely to treat COVID-19 patients or to prevent infection.
T9 897-1222 Sentence denotes The main objective of the present study is to evaluate the efficacy of hydroxychloroquine for (I) the prevention of COVID-19 or related symptoms in SARS-CoV-2-exposed subjects, such as as household members/contacts of COVID-19 patients and (II) the treatment of early-phase asymptomatic or paucisymptomatic COVID-19 patients.
T10 1223-1236 Sentence denotes TRIAL DESIGN:
T11 1237-1336 Sentence denotes This is a controlled, open label, cluster-randomized, superiority trial with parallel group design.
T12 1337-1426 Sentence denotes Subjects will be randomized either to receive hydroxychloroquine or to observation (2:1).
T13 1427-1826 Sentence denotes PARTICIPANTS: SARS-CoV-2-exposed subjects, including household members and/or contacts of COVID-19 patients and healthcare professionals (Group 1) or patients with COVID-19 (positive PCR test on a rhinopharyngeal or oropharyngeal swab for SARS-CoV-2), asymptomatic or paucisymptomatic in home situations who are not undergoing treatment with any anti COVID-19 medication (Group 2), will be enrolled.
T14 1827-1912 Sentence denotes Paucisymptomatic patients are defined as patients with a low number of mild symptoms.
T15 1913-2734 Sentence denotes All subjects must be aged ≥18 years, male or female, must be willing and able to give informed consent and must not have any contraindications to take hydroxychloroquine (intolerance or previous toxicity for hydroxychloroquine/chloroquine, bradycardia or reduction in heart rhythm with arrhythmia, ischemic heart disease, retinopathy, congestive heart failure with use of diuretics, favism or glucose-6-phosphate dehydrogenase (G6PD) deficiency, diabetes type 1, major comorbidities such as advanced chronic kidney disease or dialysis therapy, known history of ventricular arrhythmia, any oncologic/hematologic malignancy, severe neurological and mental illness, current use of medications with known significant drug-drug interactions, and known prolonged QT syndrome or current use of drugs with known QT prolongation).
T16 2735-2864 Sentence denotes The study is monocentric and will be conducted at Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS.
T17 2865-2942 Sentence denotes Subjects will be enrolled from a large epidemic region (North-Central Italy).
T18 2943-3062 Sentence denotes The Public Health Departments of several Italian regions will collaborate by identifying potentially eligible subjects.
T19 3063-3091 Sentence denotes INTERVENTION AND COMPARATOR:
T20 3092-3219 Sentence denotes The participants will be randomized (2:1 randomization) to receive either hydroxychloroquine (Arm A) or to Observation (Arm B).
T21 3220-3288 Sentence denotes Hydroxychloroquine will be administered with the following schedule:
T22 3289-3296 Sentence denotes Group1:
T23 3297-3487 Sentence denotes A loading dose hydroxychloroquine 400 mg twice daily on day 1, followed by a weekly dose of hydroxychloroquine 200 mg twice daily on days 8, 15 and 22, for a total of one month of treatment.
T24 3488-3496 Sentence denotes Group 2:
T25 3497-3614 Sentence denotes A loading dose hydroxychloroquine 400 mg twice daily on day 1 followed by 200 mg twice daily for a total of 5-7 days.
T26 3615-3802 Sentence denotes The comparator in this trial is observation given that currently neither treatment is administered to asymptomatic or paucisymptomatic subjects, nor prophylaxis is available for contacts.
T27 3803-3883 Sentence denotes Hydroxychloroquine will be shipped to subjects within 24 hours of randomization.
T28 3884-4046 Sentence denotes Given the extraordinary nature of the COVID-19 pandemic, only telephonic interviews will be carried out and electronic Patient Reported Outcomes (ePRO) completed.
T29 4047-4328 Sentence denotes During treatment, each subject will be contacted every other day for the first week and weekly thereafter (Group 2) or weekly (Group 1) by a study physician to assess early onset of any COVID-19 symptom or any adverse reaction to hydroxychloroquine and to check subject compliance.
T30 4329-4513 Sentence denotes Furthermore, all subjects will receive periodic ePROs which may be completed through smartphone or tablets to record drug self-administration and onset of any symptom or adverse event.
T31 4514-4615 Sentence denotes All subjects will be followed up for a total of 6 months by periodic telephonic interviews and ePROs.
T32 4616-4630 Sentence denotes MAIN OUTCOMES:
T33 4631-4927 Sentence denotes The primary endpoint/outcome measure for this trial is: for Group 1, the proportion of subjects who become symptomatic and/or swab-positive in each arm within one month of randomization; for Group 2, the proportion of subjects who become swab-negative in each arm within 14 days of randomization.
T34 4928-4942 Sentence denotes RANDOMIZATION:
T35 4943-5191 Sentence denotes All household members and/or contacts of each COVID-19 index case, and the COVID-19 patient himself/herself, fulfilling all inclusion criteria will be grouped into a single cluster and this cluster will be randomized (2:1) to either arm A or arm B.
T36 5192-5262 Sentence denotes Information on each subject will be recorded in specific data records.
T37 5263-5368 Sentence denotes Randomization lists will be stratified according to the following factors regarding COVID-19 index cases:
T38 5369-5371 Sentence denotes 1.
T39 5372-5461 Sentence denotes COVID-19 risk level on the basis of province of residence (high vs. low/intermediate); 2.
T40 5462-5516 Sentence denotes Index case is a healthcare professional (yes vs.no) 3.
T41 5517-5742 Sentence denotes Index case with COVID-19 treatment (yes vs. no) An independent statistician not otherwise involved in the trial will generate the allocation sequence, and COVID-19 response teams will be unaware of the allocation of clusters.
T42 5743-5843 Sentence denotes Randomization will be performed through an interactive web-based electronic data-capturing database.
T43 5844-5906 Sentence denotes An Independent Data Monitoring Committee has been established.
T44 5907-5926 Sentence denotes BLINDING (MASKING):
T45 5927-5952 Sentence denotes This study is open label.
T46 5953-5992 Sentence denotes NUMBERS TO BE RANDOMIZED (SAMPLE SIZE):
T47 5993-6153 Sentence denotes For Group 1, a sample size of about 2000 SARS-CoV-2-exposed subjects such as household members and/or contacts of COVID-19 patients will take part in the study.
T48 6154-6336 Sentence denotes Assuming around 1.5-2.0 asymptomatic household members and/or contacts for each COVID-19 patient, we expect to identify approximately 1000-1300 COVID-19 index cases to be randomized.
T49 6337-6419 Sentence denotes An interim analysis on efficacy is planned using standard alpha-spending function.
T50 6420-6708 Sentence denotes For Group 2, sufficient power for primary objective (negative swab within 14 days of randomization) will be reached given a sample size of 300 asymptomatic or paucisymptomatic COVID-19 subjects in home situations not treated for COVID-19 (25%-30% of about 1000-1300 expected index cases).
T51 6709-7010 Sentence denotes Since up to date reduced evidence about COVID-19 infection epidemiology, the continuous update of diagnostic and therapeutic approaches, the sample size estimation could be updated after a one third of population will be recruited and eventually modified according to a substantial protocol amendment.
T52 7011-7076 Sentence denotes An interim analysis at 100 enrolled COVID-19 patients is planned.
T53 7077-7241 Sentence denotes We have planned a Generalized Estimating Equation analysis, which is more efficient than a cluster level analysis, to take advantage of subject-specific covariates.
T54 7242-7325 Sentence denotes The above reported sample size analysis is therefore to be considered conservative.
T55 7326-7339 Sentence denotes TRIAL STATUS:
T56 7340-7424 Sentence denotes The current version of the PROTECT trial protocol is 'Final version, 15 April 2020'.
T57 7425-7459 Sentence denotes The study started on 9th May 2020.
T58 7460-7508 Sentence denotes The first patient was enrolled on 14th May 2020.
T59 7509-7564 Sentence denotes Recruitment is expected to last through September 2020.
T60 7565-7584 Sentence denotes TRIAL REGISTRATION:
T61 7585-7645 Sentence denotes The PROTECT trial is registered in the EudraCT database (no.
T62 7646-7740 Sentence denotes 2020-001501-24) and in ClinicalTrials.gov ( NCT04363827 ), date of registration 24 April 2020.
T63 7741-7755 Sentence denotes FULL PROTOCOL:
T64 7756-7872 Sentence denotes The full PROTECT protocol is attached as an additional file, accessible from the Trials website (Additional file 1).
T65 7873-8096 Sentence denotes In the interests of 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 (Protocol final version, 15th April 2020).
T66 8097-8177 Sentence denotes The study protocol has been reported in accordance with Standard Protocol Items:
T67 8178-8269 Sentence denotes Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).