TRV-120027
Also known as: TRV-027, TRV‑120027, TRV027, TRV120027
Source TRV-120027 at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
TRV-120027 (also called TRV‑027) is an investigational synthetic peptide that acts as a β‑arrestin‑biased ligand at the angiotensin II type‑1 receptor (AT1R). It has been tested intravenously in adults hospitalized with severe COVID‑19 to see if modulating the renin‑angiotensin system could improve respiratory outcomes.
Mechanism of Action
TRV‑120027 binds to AT1R and preferentially activates β‑arrestin‑dependent signaling while limiting the classic G‑protein pathway triggered by angiotensin II. This biased agonism is intended to reduce vasoconstrictive, pro‑inflammatory, and fibrotic effects of angiotensin II while preserving or enhancing protective pathways that may counterbalance the loss of angiotensin‑(1‑7) activity in disease.
What the Research Shows
Pre‑clinical work suggested that AT1R‑biased ligands could restore balance in the renin‑angiotensin system. The only human data to date come from a randomized, placebo‑controlled trial in 290 hospitalized COVID‑19 patients with new‑onset hypoxemia. Participants received a continuous intravenous infusion of TRV‑027 (12 mg/h) for five days. The primary endpoint—oxygen‑free days at 28 days—did not differ from placebo (adjusted odds ratio 0.74, 95 % credible interval 0.48–1.13). All‑cause mortality at 28 days was numerically higher in the TRV‑027 group (20.6 % vs 12.9 %) but the credible interval (0.75–3.08) included no effect. Safety outcomes (allergic reactions, new renal replacement therapy, hypotension) were similar between groups. The trial stopped early for futility, and no other clinical studies of TRV‑120027 have been published.
Reported Benefits
Current evidence does not demonstrate a clinical benefit of TRV‑120027 in severe COVID‑19. The trial showed no improvement in oxygen‑free days and an uncertain effect on mortality, with safety comparable to placebo. No proven advantages exist for any other indication at this time.
Limitations of the Evidence
Findings are limited to a single, early‑stopped trial in a specific patient population (hospitalized COVID‑19 with hypoxemia). The sample size was modest, and the credible intervals were wide, leaving uncertainty about modest effects. No data exist for chronic use, other diseases, or different dosing regimens, and pre‑clinical results have not yet translated into clinical benefit.
Safety Considerations
In the COVID‑19 trial, adverse events tracked (allergic reactions, initiation of kidney replacement therapy, hypotension) occurred at similar rates in the TRV‑027 and placebo arms, indicating no major safety signal in the short‑term infusion. Long‑term safety, rare events, or risks in other patient groups have not been evaluated.
How It Is Administered
TRV‑120027 is delivered by continuous intravenous infusion, typically at 12 mg per hour for a five‑day course in the studied trial. It is formulated for IV use only; no oral or other routes have been reported.
Routes of Administration
Goals & Uses
- Cardiomyocyte cytoprotectionCardioprotectionLow
- Acute decompensated heart failureCardiovascularModerate
- Reduction of dyspnea in acute heart failureCardiovascular / HemodynamicModerate
- Reduction of preload/afterloadHemodynamicModerate
- Reduction of cardiac preload and afterloadCardiovascular / HemodynamicModerate
- Renal protection during AHF treatmentRenal / Organ ProtectionLow
Contraindications
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
- Concurrent use of potent vasodilatorsPharmacologicModerate
- Hypotension (severe)HemodynamicHigh
- Severe bilateral renal artery stenosisRenalHigh
- Severe hypotensionCardiovascularHigh
Adverse Effects
- HeadacheNeurologicUncommonPain in the head or upper neck
- HypotensionCardiovascularCommonLow blood pressure
- NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
- DizzinessNeurologicCommonFeeling faint, lightheaded, or unsteady
- Worsening renal functionRenalUncommon
Drug Interactions
- Antihypertensive agentsModerate
- Angiotensin Receptor Blockers (ARBs)Low
- ACE inhibitorsModerate
- Potassium-sparing diureticsModerate
Population Constraints
- Renal impairmentOrgan ImpairmentRelative
- Pediatric populationAgeRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveAbsolute
- Severe hepatic impairmentOrgan ImpairmentRelative
Regulatory Status
- European UnionInvestigationalNo marketing authorization granted
- United StatesInvestigationalPhase 2 completed; not submitted for FDA approval
- United KingdomUnapprovedNo regulatory submission or approval in the United Kingdom.
Completed Phase 2 studies; not submitted for marketing authorization in major jurisdictions.
Evidence & Sources
- Journal ArticleLowSelf WH, et al.2023-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of molecule is TRV‑120027?
It is a synthetic peptide designed to act as a β‑arrestin‑biased agonist at the angiotensin II type‑1 receptor, aiming to modulate the renin‑angiotensin system.
Has TRV‑120027 been approved for any medical use?
No. It remains an investigational agent and has only been studied in a clinical trial for severe COVID‑19, where it did not show efficacy.
How was TRV‑120027 administered in the trial?
Patients received a continuous intravenous infusion at a rate of 12 mg per hour for five consecutive days.
Did the trial show any safety concerns?
Safety outcomes such as allergic reactions, new kidney replacement therapy, and hypotension were similar to placebo, indicating no obvious short‑term safety issues in the studied population.
Could TRV‑120027 be useful for conditions other than COVID‑19?
At present there is no clinical evidence to support use in other diseases; further research would be needed to explore any potential benefits.
What is TRV-120027?
TRV-120027 (also called TRV‑027) is an investigational synthetic peptide that acts as a β‑arrestin‑biased ligand at the angiotensin II type‑1 receptor (AT1R). It has been tested intravenously in adults hospitalized with severe COVID‑19 to see if modulating the renin‑angiotensin system could improve respiratory outcomes.
What is TRV-120027 used for?
TRV-120027 is educationally associated with: Cardiomyocyte cytoprotection, Acute decompensated heart failure, Reduction of dyspnea in acute heart failure, Reduction of preload/afterload, Reduction of cardiac preload and afterload, Renal protection during AHF treatment. Educational only — not medical advice.
How is TRV-120027 administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of TRV-120027?
Reported adverse effects include: Headache, Hypotension, Nausea, Dizziness, Worsening renal function. This list is not exhaustive — consult a qualified clinician.
Who should avoid TRV-120027?
Recorded contraindications: Pregnancy, Concurrent use of potent vasodilators, Hypotension (severe), Severe bilateral renal artery stenosis, Severe hypotension. Consult a qualified clinician before use.