Trial reportNature medicine2026
The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial.
Trial report in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06142383 (A Multi-center, Randomized, Placebo- and Active-controlled, Parallel-group, 24-week Proof of Concept and Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Heart Failure), which is not on this map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-center, Randomized, Placebo- and Active-controlled, Parallel-group, 24-week Proof of Concept and Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Heart Failure
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Therapies targeting the natriuretic peptide system have the potential to reduce death or heart failure events in heart failure with reduced ejection fraction. Here we assess XXB750, a human monoclonal antibody activating natriuretic peptide receptor 1, in patients with heart failure. Patients with heart failure and a left ventricular ejection fraction <50% were enrolled. Those patients who were on background angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment were randomized to receive 60 mg XXB750, 120 mg XXB750 or placebo in a blinded fashion or sacubitril/valsartan treatment in an open-label fashion. Those patients on background sacubitril/valsartan treatment were randomized to either 60 mg XXB750, 120 mg XXB750 or placebo treatment in a blinded fashion. The primary endpoint was the change in NT-proBNP levels at 16 weeks after treatment initiation, and safety was also assessed. We randomized 136 participants (70% male, 30% female) to 60 mg XXB750 (n = 26), 120 mg XXB750 (n = 55), matching placebo (n = 29) or sacubitril/valsartan (n = 25). At 16 weeks, NT-proBNP levels rose (ratio of change from baseline 1.34, 95% confidence interval (CI) 1.07-1.66) and cyclic guanosine monophosphate (cGMP) levels declined (ratio of change from baseline 0.77, 95% CI 0.65-0.91) in the pooled XXB750 arms, whereas NT-proBNP levels declined from baseline (ratio of change from baseline 0.70, 95% CI 0.45-1.10), and cGMP levels rose (ratio of change from baseline 1.38, 95% CI 1.13-1.69) in the sacubitril/valsartan arm. Death or worsening heart failure events occurred more frequently in those receiving XXB750 (25%) compared with those receiving sacubitril/valsartan (8%), or placebo (0%). Because of the excess heart failure events in participants receiving XXB750, the data monitoring committee recommended stopping the trial prematurely. In contrast to the expected mechanism of drug action, XXB750 treatment led to increased NT-proBNP levels, lowered cGMP levels and more worsening heart failure events, suggesting that XXB750 may paradoxically behave as a functional antagonist of endogenous natriuretic peptides in patients with heart failure. Clinicaltrials.gov registration: NCT06142383 .
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.