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1.
Topics in Antiviral Medicine ; 30(1 SUPPL):174, 2022.
Article in English | EMBASE | ID: covidwho-1881008

ABSTRACT

Background: Remdesivir (RDV), a potent nucleotide inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, effectively reduces COVID-19 related hospitalization in outpatients at high risk for progression to severe disease. However, limited data exist on the safety profile of RDV in this population. Methods: We conducted a Phase III placebo-controlled study evaluating a 3-day regimen of RDV in non-hospitalized patients who are at risk for disease progression (age>60 years or underlying comorbid condition). Patients were randomly assigned 1:1 to receive intravenous RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo (PBO). The primary safety endpoint was the proportion of patients with treatment-emergent adverse events (AEs). AEs were evaluated through day 28 and lab abnormalities were evaluated through day 14. Results: 562 patients were randomized and initiated treatment (279, RDV;283, placebo). Baseline characteristics were balanced between groups. Thirty percent were ≥60 years old and most common comorbidities were diabetes mellitus (62%), obesity (56%;median BMI, 30.7 kg/m2), and hypertension (48%). RDV was well tolerated with a similar rate of any AEs between groups (Table). Patients treated with RDV had fewer Grade ≥3 and serious AEs (SAEs) compared to PBO, but had more study-drug related AEs, with the most common one being nausea (18 [6.5%] in RDV vs. 10 [3.5%] in PBO). Grade 3 or higher ALT elevation was reported in 1 (0.4%) RDV vs. 2 (0.7%) PBO treated patients. Median change from baseline in AST, ALT, and bilirubin was similar between groups (Table). Grade 3 or higher decrease in creatinine clearance (CrCl) occurred more often in RDV vs. to PBO treated patients (5.6% vs 1.9% respectively). Most decreases in creatinine clearance occurred within the normal serum creatinine range, occurred after completion of RDV therapy, and resolved on follow-up. Median changes in CrCl from baseline were similar between groups and no renal AEs were reported (Table). Incidence of cardiac-related AEs was similar between RDV and PBO groups. All bradycardia events occurred in the PBO group. No patient experienced a serious AE or drug discontinuation due to hypersensitivity. Conclusion: Treatment with RDV was safe and well tolerated in non-hospitalized patients with risk factors for COVID-19 disease progression. Patients in the RDV group had similar type, incidence, and severity of AEs and lab abnormalities as those receiving PBO.

2.
Topics in Antiviral Medicine ; 30(1 SUPPL):175, 2022.
Article in English | EMBASE | ID: covidwho-1880683

ABSTRACT

Background: There is currently no approved treatment for patients with COVID-19 who have not been hospitalized, a setting in which early intervention may curb progression to more severe disease requiring hospitalization. We report longitudinal biomarker sampling from a Phase III (PINETREE) clinical trial to evaluate prognostic biomarkers of COVID-19 and to better understand the early remdesivir (RDV) treatment response. Methods: A Phase III, randomized, double-blind, placebo controlled, multicenter study was conducted to evaluate the efficacy and safety of RDV for outpatients with early stage COVID-19 who are at higher risk of disease progression (NCT04501952). Inclusion criteria were ≥60 years of age or ≥12 years of age with at least one risk factor for severe COVID-19 disease. All individuals had ≤7 days of symptoms prior to randomization. A total of 562 participants were randomized 1:1 to RDV or placebo. Serum and plasma were collected for biomarker analyses in 312 patients at days 1, 3, and 14 post-treatment. All biomarker values were adjusted for baseline age and stratified by sex. Results: RDV demonstrated an 87% reduction in risk for the primary composite endpoint of COVID-19-related hospitalization or all-cause death by day 28 (0.7% [2/279]) compared with placebo (5.3% [15/283]) (p=0.008). RDV treatment was associated with improved clinical outcomes in participants with higher risk of hospitalization or death from COVID-19, including individuals ≥60 years of age, males, and/or those with diabetes, obesity, and hypertension. Furthermore, we found that biomarkers associated with inflammation and coagulation, including lactate dehydrogenase (p<0.001) and procalcitonin (p<0.001), were prognostic for COVID-19 related hospitalization or all-cause death by day 28. Finally, we found that RDV improved some biomarkers associated with COVID-19 severity by day 3 of treatment, including peripheral lymphopenia, monocyte count, and decreased neutrophil-to-lymphocyte ratio compared to placebo (pWilcox<0.05). Conclusion: Our findings suggest that RDV treatment improves COVID-19 outcomes in high-risk SARS-CoV-2 infected individuals, particularly in those ≥60 years of age, male, and/or with diabetes, obesity, and hypertension. Biomarkers of COVID-19 severity that were prognostic for poor outcomes were identified in early infection. Furthermore, our results suggest that RDV treatment leads to more rapid recovery in the lymphopenia that is commonly associated with more severe COVID-19.

3.
Topics in Antiviral Medicine ; 30(1 SUPPL):296-297, 2022.
Article in English | EMBASE | ID: covidwho-1879908

ABSTRACT

Background: Remdesivir (RDV) has been shown to shorten time to recovery in hospitalized adults with COVID-19. Some children who develop COVID-19 require hospitalization. Here we characterize the safety profile of RDV in 53 pediatric patients age 28 days to <18 years and describe clinical and virologic outcomes. Methods: CARAVAN (NCT04431453) is an ongoing open-label, single arm study of RDV in hospitalized patients <18 years with PCR-confirmed COVID-19. IV RDV was given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 and 8 (<18y, weight ≥40kg) or 5mg/kg on Day 1 followed by 2.5mg/kg daily in Cohorts 2-4 (28 days to <18y, stratified by weight). Safety was assessed by adverse events (AEs) and lab tests (hematology, chemistry, urine, inflammatory, coagulation). Clinical outcomes included improvement on a 7-point ordinal scale, time to discharge, and oxygenation modality. Virologic outcomes included days to confirmed negative SARS-CoV-2 PCR (defined as 2 consecutive negative results). Results: At enrollment, median (IQR) age was 7y (2, 12) and weight was 24.6 (12.8, 55.1) Kg, 57% were female, 76% required supplemental oxygen, including 23% on invasive ventilation and 34% on high-flow oxygen (Table). Median number of RDV doses was 5 (4,8). Most patients (72%) experienced ≥1 AE;most common was constipation (17%). Serious AEs were reported for 21% of patients and none were study-drug related. Two patients with baseline transaminitis had non-serious AE of increased ALT contributing to premature discontinuation. Two patients died within the 30-day study period. Grade ≥ 3 lab abnormalities were reported in 42%;most common being decreased haemoglobin (n=9) and decreased eGFR levels (n=7). No safety trends related to RDV were apparent. In total, 85% showed clinical improvement on the 7-point ordinal scale by last assessment. Median (IQR) time to discharge was 8 (5, 17) days. By last assessment, 8% required supplemental oxygen, all of whom were invasively ventilated. Time to confirmed negative SARS-CoV-2 PCR CoV-2 PCR was 5 and 7 days from nasal/oropharyngeal samples in cohort 2 and 3, respectively, and not estimable in the other cohorts. Conclusion:RDV was safe and well tolerated among children 28 days to <18y treated for COVID-19. Overall, no safety trends for RDV were apparent and a high proportion, 85%, had clinical improvement. The study is ongoing with enrolment of full term and preterm neonates pending dose determination.

4.
Open Forum Infectious Diseases ; 8(SUPPL 1):S806-S807, 2021.
Article in English | EMBASE | ID: covidwho-1746277

ABSTRACT

Background. Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540-9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19. Methods. Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID-19 hospitalization or all-cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment-emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results. 562 patients underwent randomization and started their assigned treatment (279, RDV;283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%;median BMI, 30.7), and hypertension (48%). Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13;95% CI, 0.03 - 0.59;p = 0.008;Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID-19-related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19;95% CI, 0.07 - 0.56;p = 0.002;Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1);the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion. A 3-day course of IV RDV was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients.

5.
Open Forum Infectious Diseases ; 7(SUPPL 1):S304-S305, 2020.
Article in English | EMBASE | ID: covidwho-1185837

ABSTRACT

Background: COVID-19 has spread rapidly: from the first case in Dec 2019, the declaration of a global pandemic in Mar 2020, to Jun 18, 2020 with >8 M confirmed cases and >400,000 deaths worldwide. Throughout this rapid spread, Gilead has focused on contributing antiviral expertise and resources to help patients (pts) and communities fighting COVID-19 Methods: Gilead is supporting the efforts of governments, partnering with professionals, and community-based org., and collaborating with healthcare providers to accelerate research and access to remdesivir (RDV), the first medicine with demonstrated efficacy in treatment of COVID-19. This is a review of the programs initiated in RDV research, access, research grants and collaborative education Results: In Jan 2020 Gilead began working with government and regulatory authorities to make RDV accessible to pts globally through the compassionate use and expanded access programs. These programs has treated >2000 COVID-19 pts. By Feb 2020, several phase 3 randomized trials on RDV were initiated. Based on trials completed and published data (n= >2000), RDV was granted emergency use authorization in the US on May 1, 2020 with full approval in 5 countries thereafter and several under review elsewhere. Collectively there will be >12,000 pts enrolled in RDV clinical programs by Dec 2020. Increasing manufacturing of RDV began at-risk in Jan 2020. By May 2020 Gilead has decreased production time, increased supply and committed to donating all its 1.5 M doses. Under the licensing agreements with generic drug manufacturers, RDV will be available in 127 countries upon approval. Gilead has committed to supporting research grants to enhance the understanding of the clinical course and outcomes in vulnerable population, long-term sequelae, and evaluate real world safety and effectiveness of COVID-19 therapies. Finally, Gilead has provided corporate grants to support the efforts of community-based orgs and public health entities to expand education on COVID-19 Conclusion: Gilead has initiated a global, multifaceted rapid response that reflects the unprecedented emergency posed by SARS-COV-2. This includes increasing RDV production, access, timely initiation of phase 3 RDV trials, and establishment of grants programs for community projects, research and education.

6.
Indian Journal of Community Health ; 32(4):713-+, 2020.
Article in English | Web of Science | ID: covidwho-1100580

ABSTRACT

Background: Lockdown due to COVID-19 pandemic has an effect on all the dimensions of health. Previous epidemics and pandemics had made a catastrophic impact on mental wellbeing of general public. Methods: A cross sectional online study was carried out in the month of May. Data collection was done using Google form which contained semi-structured questionnaire. Results: Total 450 individuals participated in the study. About one-fourth of the participants felt depressed (28.9%) listening to the constant news updates about corona virus. Almost half of participants (50.7%) had altered eating habits. Nearly one-third of the participants had difficulty (35.1%) in falling asleep. Conclusion: This study reports that there is a negative impact on psychosocial health of general public who were confined to their homes due to COVID-19 pandemic in the country.

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