COVID-19 Publications

31

Aug, 2020

COVID-19 Pandemic: Perspective of an Italian Tertiary Care Pediatric Center

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Abstract Since February 2020, Italy has been faced with the dramatic spread of novel Coronavirus SARS-CoV-2. This impetuous pandemic infection forced many hospitals to reorganize their healthcare systems. Predicting a rapid spread of the SARS-CoV-2 virus within our region, the Department for Women’s and Children’s Health promptly decided (i) to revise the distribution of the clinical areas in order to create both designated COVID-19 and COVID-19-free areas with their own access, (ii) to reinforce infection prevention control (IPC) measures for all healthcare workers and administrative staff and (iii) to adopt the new “double-gate approach”: a phone call pre-triage and nasopharyngeal swab for SARS-CoV-2 detection before the admission of all patients and caregivers. Between 21 February 2020 till 04 May 2020, only seven physicians, two nurses and two of the administrative staff resulted positive, all during the first week of March. No other cases of intra-department infection were documented among the healthcare workers since all the preventive procedures described above were implemented. It is predicted that similar situations can happen again in the future, and thus, it is necessary to be more prepared to deal with them than we were at the beginning of this COVID-19 pandemic.

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25

Aug, 2020

COVID-19 and multisystem inflammatory syndrome in children and adolescents

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Abstract As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development.

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21

Aug, 2020

Pediatric transplantation in Europe during the COVID-19 pandemic: early impact on activity and healthcare

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Abstract The current pandemic SARS-CoV-2 virus has required an unusual allocation of resources that can negatively impact of chronically ill patients and high-complexity procedures. Across the European reference network on pediatric transplantation (ERN-TransplantChild) we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell (HSCT) transplantation. The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified, restricted to selected ones and to the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients and their families.

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13

Aug, 2020

A reason to SMILE – we reached Last Patient Last Visit

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Last Patient Last Visit (LPLV) completed for the Penta 17 Strategy for Maintenance of HIV suppression with integrase inhibitor + darunavir/ritonavir in children (SMILE) trial.

The Penta sponsored trial, SMILE, has completed its last patient last visit. This exciting news comes to us following the closure of patient enrolment for SMILE last year, where all participants recruited were followed up for a minimum of 48 weeks until the last participant enrolled reached 48 weeks of follow-up on 11 August 2020.

This brings the SMILE trial to a close, and is an important milestone for the trial. Our congratulations and thanks go to all the participants and families, the clinicians and sites involved as well as the clinical trial units of the study, INSERM-SC10MRC-CTU at UCL and PHPT for their collaboration!

SMILE is a multicentre randomised study evaluating safety and antiviral effect of a once daily integrase inhibitor administered with darunavir/ritonavir compared to standard of care among HIV-1 infected, virologically suppressed paediatric participants. Participants from 32 sites spread across 11 countries in Europe, Asia, Africa and South America have taken part in the study. The trial has been funded by Janssen, Gilead and ViiV Healthcare.

 

6

Aug, 2020

ODYSSEY trial data published in Lancet – shows increase in treatment options for older children living with HIV

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Results from from the ongoing P1093 and ODYSSEY (PENTA20) studies, published in The Lancet HIV journal, show that children over 20kg in weight can safely take adult doses (50mg) of the anti-HIV drug dolutegravir. With over half of children living with HIV globally weighing at over 20kg, this expands treatment options and simplifies treatment for children.

These data have already had impact!

They have been used to gain FDA approval for use of the adult dosage of the dolutegravir (50mg) in children weighing ≥20kg, in June 2020. Thus, allowing immediate access to adult dolutegravir formulation procured and available in many countries for the majority of children living with HIV. Further dolutegravir paediatric submissions are currently under review by the European Medicines Agency (EMA) and other regulatory approvals around the world. These results have also informed the WHO 2019 dolutegravir paediatric dosing guidelines.

The results uncovered are pivotal in the fight against HIV! Building on these results the ODYSSEY team can work to simplify health services and ensure timely access to optimal antiretroviral therapies for children living with HIV around the world.

ODYSSEY is a multi-centre, randomised clinical trial to assess the efficacy and toxicity of dolutegravir plus 2 NRTI versus standard of care among HIV positive children and adolescents. Penta is the sponsor of this study, which is funded by ViiV Healthcare. The study anticipates 700 patients to be enrolled across 30 sites in Europe, Africa and Asia. The results from the main ODYSSEY trial are expected in 2021.

Read the full article in The Lancet HIV and hear directly from Di Gibb and Anna Turkova from the Medical Research Council Clinical Trials Unit at University College London, discussing paediatric HIV treatment and the importance of the ODYSSEY results for children living with HIV in the Lancet HIV podcast.

6

Aug, 2020

Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial

 

Authors: Bollen P,  Moore CL ,  Mujuru H et al; the ODYSSEY trial team

Published in: LANCET HIV. 2020;8:e533-e544

Background Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in patients enrolled in the ODYSSEY-trial to evaluate simplified dosing in children with HIV.

Methods We did pharmacokinetic and safety substudies within the open-label, multicentre, randomised ODYSSEY trial (NCT02259127) of children with HIV starting treatment in four research centres in Uganda and Zimbabwe. Eligible children were randomised to dolutegravir in ODYSSEY and weighed 20 kg to less than 40 kg. In children weighing 20 kg to less than 25 kg, we assessed dolutegravir’s pharmacokinetics in children given once daily 25 mg film-coated tablets (approved by the SRAs at the time of the study) in part one of the study, and 50 mg film-coated tablets (adult dose) or 30 mg dispersible tablets in part two of the study. In children weighing 25 kg to less than 40 kg, we also assessed dolutegravir pharmacokinetics within-subject on film-coated tablet doses of 25 mg or 35 mg once daily, which were approved by the SRAs for the children’s weight band; then switched to 50 mg film-coated tablets once daily. Steady-state 24 h dolutegravir plasma concentration-time pharmacokinetic profiling was done in all enrolled children at baseline and 1, 2, 3, 4, 6, and 24 h after observed dolutegravir intake. Target dolutegravir trough concentrations (Ctrough) were based on reference adult pharmacokinetic data and safety was evaluated in all children in the corresponding weight bands who consented to pharmacokinetic studies and received the studied doses.

Findings Between Sept 22, 2016, and May 31, 2018, we enrolled 62 black-African children aged from 6 years to younger than 18 years (84 pharmacokinetic-profiles). In children weighing 20 kg to less than 25 kg taking 25 mg film-coated tablets, the geometric mean (GM) Ctrough (coefficient of variation) was 0·32 mg/L (94%), which was 61% lower than the GM Ctrough of 0·83 mg/L (26%) in fasted adults on dolutegravir 50 mg once-daily; in children weighing 25 kg to less than 30 kg taking 25 mg film-coated tablets, the GM Ctrough was 0·39 mg/L (48%), which was 54% lower than the GM Ctrough in fasted adults; and in those 30 kg to less than 40 kg taking 35 mg film-coated tablets the GM Ctrough was 0·46 mg/L (63%), which was 45% lower than the GM Ctrough in fasted adults. On 50 mg film-coated tablets or 30 mg dispersible tablets, Ctrough was close to the adult reference (with similar estimates on the two formulations in children in the 20 to <25 kg weight band), with total exposure (area under the concentration-time curve from 0 h to 24 h) in between reference values in adults dosed once and twice daily, where safety data are reassuring, although maximum concentrations were higher in children weighing 20 kg to less than 25 kg than in the twice-daily adult reference. Over a 24-week follow-up period in 47 children on 30 mg dispersible tablets or 50 mg film-coated tablets, none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymptomatic neutropenia) were considered related to dolutegravir.

Interpretation Adult dolutegravir 50 mg film-coated tablets given once daily provide appropriate pharmacokinetic profiles in children weighing 20 kg or more, with no safety signal, allowing simplified practical dosing and rapid access to dolutegravir. These results informed the WHO 2019 dolutegravir paediatric dosing guidelines and have led to US Food and Drug Administration approval of adult dosing down to 20 kg.

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