Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial

What Was Tested

Researchers studied VIP (Vasoactive Intestinal Peptide) in this randomized controlled trial publication.

Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Who Took Part

The abstract describes 19 patients taking part.

The age groups tagged for this paper are adults and middle-aged adults, both men and women.

Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure.

Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents.

How the Study Was Run

The researchers set it up as a randomized and placebo-controlled study.

The patients were allocated by chance, so the VIP (Vasoactive Intestinal Peptide) group and the comparison group should start out alike.

The comparison arm used a placebo, so changes seen with VIP (Vasoactive Intestinal Peptide) could be set against what happens without it.

A time span of 4 days appears in the methods.

TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Participants were randomly assigned with a web-based application.

For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated.

For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo.

For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes.

What Was Measured

For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead.

Mortality up to day 90 was a key secondary outcome.

Topics PubMed links to this paper include COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Respiratory Insufficiency, Oxygen, Drug Combinations and Phentolamine.

What This Means in Plain Language

The paper is a randomized and placebo-controlled study of VIP (Vasoactive Intestinal Peptide) in 19 patients over 4 days.

With fewer than 40 people, it is a small study, so it is better read as an early signal for further research than as a settled answer.

Results are reported in around 11 sentences of the abstract; we leave them to the paper itself rather than summarise them.

The publication is from 2023 (The Lancet. Respiratory medicine), a journal based in England.

More context: the VIP (Vasoactive Intestinal Peptide) compound page, all human trials.