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

Brown, SM; Barkauskas, CE; Grund, B; Sharma, S; Phillips, AN; Leither, L; Peltan, ID; Lanspa, M; Gilstrap, DL; Mourad, A; Lane, K; Beitler, JR; Serra, AL; Garcia, I; Almasri, E; Fayed, M; Hubel, K; Harris, ES; Middleton, EA; Barrios, MAG; Mathews, KS; Goel, NN; Acquah, S; Mosier, J; Hypes, C; Salvagio Campbell, E; Khan, A; Hough, CL; Wilson, JG; Levitt, JE; Duggal, A; Dugar, S; Goodwin, AJ; Terry, C; Chen, P; Torbati, S; Iyer, N; Sandkovsky, US; Johnson, NJ; Robinson, BRH; Matthay, MA; Aggarwal, NR; Douglas, IS; Casey, JD; Hache-Marliere, M; Georges Youssef, J; Nkemdirim, W; Leshnower, B; Awan, O; Pannu, S; O'Mahony, DS; Manian, P; Awori Hayanga, JW; Wortmann, GW; Tomazini, BM; Miller, RF; Jensen, JU; Murray, DD; Bickell, NA; Zatakia, J; Burris, S; Higgs, ES; Natarajan, V; Dewar, RL; Schechner, A; Kang, N; Arenas-Pinto, A; Hudson, F; Ginde, AA; Self, WH; Rogers, AJ; Oldmixon, CF; Morin, H; Sanchez, A; Weintrob, AC; Cavalcanti, AB; Davis-Karim, A; Engen, N; Denning, E; Taylor Thompson, B; Gelijns, AC; Kan, V; Davey, VJ; Lundgren, JD; Babiker, AG; Neaton, JD; Lane, HC; ACTIV-3b/Therapeutics for Severely Ill Inpatients with COVID-19 (TESICO) Study Group

doi:10.1016/s2213-2600(23)00147-9

Respiratory failure & ventilation

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

Lancet Respir MedPublished 19 Jun 2023Randomised controlled trial

Primary result · Better category of ordinal outcome, aviptadil vs placeboResultOdds ratio 1.11 95% CI 0.80–1.55

Aviptadil trial stopped for futility on May 25, 2022 (data and safety monitoring board)

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Authors' conclusion

Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo.

Study context

Population: Hospitalised adults with acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection, within 4 days of onset, 28 US sites461 aviptadil mITT
Participants: 473 adults

Comparison: Aviptadil vs placebo; remdesivir vs placebo
Aviptadiln = 231
Placebon = 230reference
Primary endpoint: Six-category ordinal outcome:
From at home
Off oxygen ≥77 days to dead
Follow-up: Up to day 90

Methodological detailsplacebo-controlled, 2 × 2 factorial, multicentre (28 sites), stratified randomisation, Remdesivir trial stopped on June 9, 2022, due to slow enrolment (87 randomised)

Placebo-controlled
2 × 2 factorial
Multicentre (28 sites)
Stratified randomisation
Remdesivir trial stopped on June 9, 2022, due to slow enrolment (87 randomised)

Primary result

As reported in the abstract

Better category of ordinal outcome, aviptadil vs placebo

Odds ratio

1.11

95% CI 0.80–1.55

P = 0.54

Aviptadil vs Placebo

OR 1.11 (95% CI 0.80–1.55); P = 0.54

Secondary outcomes

Outcome	Aviptadil	Placebo	← Lower risk with aviptadil ←→ Higher risk with aviptadil →	HR (95% CI)	P value
Mortality (key secondary) · up to day 90Cumulative percentage	38%	36%	0.512	1.04 (0.77–1.41)	P = 0.78
			0.512Hazard ratio (log scale)

Safety

Outcome	Aviptadil	Placebo	← Lower odds with aviptadil ←→ Higher odds with aviptadil →	OR (95% CI)	P value
Primary safety outcome: death, serious AEs, organ failure, serious infection, or grade 3/4 AEs · up to day 5	63%	56%	0.512	1.40 (0.94–2.08)	P = 0.10
			0.512Odds ratio (log scale)

Reference

Authors: Brown SM, Barkauskas CE, Grund B, Sharma S, Phillips AN, Leither L, et al.
All 88 authors
Brown SM, Barkauskas CE, Grund B, Sharma S, Phillips AN, Leither L, Peltan ID, Lanspa M, Gilstrap DL, Mourad A, Lane K, Beitler JR, Serra AL, Garcia I, Almasri E, Fayed M, Hubel K, Harris ES, Middleton EA, Barrios MAG, Mathews KS, Goel NN, Acquah S, Mosier J, Hypes C, Salvagio Campbell E, Khan A, Hough CL, Wilson JG, Levitt JE, Duggal A, Dugar S, Goodwin AJ, Terry C, Chen P, Torbati S, Iyer N, Sandkovsky US, Johnson NJ, Robinson BRH, Matthay MA, Aggarwal NR, Douglas IS, Casey JD, Hache-Marliere M, Georges Youssef J, Nkemdirim W, Leshnower B, Awan O, Pannu S, O'Mahony DS, Manian P, Awori Hayanga JW, Wortmann GW, Tomazini BM, Miller RF, Jensen JU, Murray DD, Bickell NA, Zatakia J, Burris S, Higgs ES, Natarajan V, Dewar RL, Schechner A, Kang N, Arenas-Pinto A, Hudson F, Ginde AA, Self WH, Rogers AJ, Oldmixon CF, Morin H, Sanchez A, Weintrob AC, Cavalcanti AB, Davis-Karim A, Engen N, Denning E, Taylor Thompson B, Gelijns AC, Kan V, Davey VJ, Lundgren JD, Babiker AG, Neaton JD, Lane HC, ACTIV-3b/Therapeutics for Severely Ill Inpatients with COVID-19 (TESICO) Study Group
Journal: The Lancet Respiratory Medicine
Published: 19 Jun 2023
DOI: 10.1016/s2213-2600(23)00147-9
PubMed: 37348524
Registration: NCT04843761

Topic: Respiratory failure & ventilation
Also indexed: Sepsis & infection

Intervention details

Aviptadil: daily 12-h IV infusion for 3 days (600, 1200, 1800 pmol/kg on days 1–3)
Placebo: aviptadil matched saline placebo

Key notes

Stratified by baseline disease severity
Modified intention-to-treat

Original publication

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. Published 19 June 2023. doi:10.1016/s2213-2600(23)00147-9

Read the original article ↗

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