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Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial

Por: Bokoch · M. P. · Tran · A. T. · Brinson · E. L. · Marcus · S. G. · Reddy · M. · Sun · E. · Roll · G. R. · Pardo · M. · Fields · S. · Adelmann · D. · Kothari · R. P. · Legrand · M.
Introduction

Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.

Methods and analysis

This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg-1 min-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test.

Ethics and dissemination

The trial protocol was approved by the local Institutional Review Board (#20–30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal.

Trial registration number

ClinicalTrials.govNCT04901169

Assessing the burden of HPV-related head and neck cancers in mainland China: protocol of a nationwide, multisite, cross-sectional study

Por: Wang · W. · Song · C. · Su · Z. · Kothari · S. · Chen · Y.-T. · Liu · Y. · Wu · S.-Y. · Panchal · R. · Morais · E. · Zhang · S.-K. · Yin · J. · Qiao · Y.-L. · Roberts · C.
Background

Persistent human papillomavirus (HPV) infection is a known cause of a subset of head and neck cancers (HNCs). In the last two decades, the proportion of HNCs attributable to HPV infection has increased worldwide, notably the oropharyngeal cancers. However, the trend of HPV-related HNC burden is not clearly understood yet in China. Thus, the absolute burden of HPV-related head and neck cancers in China (BROADEN-China) will be conducted to estimate the proportion of HNCs attributable to HPV infection, per anatomic site, by genotype, in three time periods (2008–2009, 2013–2014 and 2018–2019).

Methods and analysis

BROADEN-China is a nationwide, multisite, cross-sectional study. A stratified, multistage, non-randomised cluster sampling method will be used to select 2601 patients with HNC from 14 hospitals across seven regions, based on population density in China. Patients with formalin-fixed paraffin-embedded tissue samples collected prior to treatment induction during three time periods will be included, and factors (eg, smoking status, alcohol consumption, betel nut chewing, Epstein-Barr virus, teeth loss, etc) associated with HNC will be assessed. HPV testing (HPV-DNA, HPV-mRNA and p16INK4a immunohistochemistry) and histological diagnosis of the tissue samples will be conducted at a central laboratory.

The study protocol and all required documents have been submitted for review and approval to the Independent Ethics Committees of all the participating sites. The informed consent was waived for all participants and all the recorded data will be treated as confidential.

We have included 14 hospitals as our participating sites, of which Henan Cancer Hospital is the leading site. The study has been approved by the independent ethics committees of the leading site on 3 December 2020. The other 13 participating site names of ethics committee and IRB that have approved this study.

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