# What did the ASCEND-HF trial measure? Nesiritide in acute heart failure Updated 2026-10-16. ASCEND-HF (NCT00475852) was a large trial of nesiritide, a laboratory-made form of the hormone B-type natriuretic peptide. The trial compared nesiritide with a placebo, a dummy treatment, in 7,141 patients in hospital with acute heart failure. ASCEND-HF measured dyspnoea (breathlessness) at 6 and 24 hours, and death or a return to hospital for heart failure within 30 days. The breathlessness result missed the bar set in advance. | | | | --- | --- | | Trial name | ASCEND-HF, Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure | | Registry number | [NCT00475852](https://clinicaltrials.gov/study/NCT00475852), Phase 3, results posted | | Sponsor | Scios, Inc. (ClinicalTrials.gov) | | Dates | Started May 2007; completed March 2011 (ClinicalTrials.gov) | | Participants | 7,141 patients hospitalised with acute heart failure ([O'Connor et al., 2011](https://pubmed.ncbi.nlm.nih.gov/21732835/)) | | Comparison | Nesiritide or placebo for 24 to 168 hours, added to standard care (O'Connor et al., 2011) | | Co-primary endpoints | Dyspnoea at 6 and 24 hours; death or heart-failure rehospitalisation within 30 days (O'Connor et al., 2011) | | Published | N Engl J Med, 7 July 2011 | Breathlessness is one of the first things a failing heart makes you notice, and it is the symptom doctors wanted a new drug to ease. Nesiritide was approved in the United States in 2001 with that aim, according to its [FDA record](https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020920). [The natriuretic peptides hub](/learn/natriuretic-peptides) covers the hormone family it comes from, and this guide covers the largest trial that tested it. A trial result only means something next to the question it asked. So this page lists what ASCEND-HF measured first, then the numbers, then the limits. It reports what the published abstract and the registry record state. ## What was the ASCEND-HF trial? ASCEND-HF was a large, late-stage (Phase 3) trial. It included 7,141 patients in hospital with acute heart failure. Each patient got either nesiritide or a placebo for 24 to 168 hours, on top of standard care. The trial was randomised: chance decided which group each patient joined, like a coin toss. It was also double-blind: neither patients nor doctors knew who was in which group during the comparison. The registry lists Scios, Inc. as the sponsor. The trial started in May 2007 and was completed in March 2011. Nesiritide is recombinant human B-type natriuretic peptide, meaning the BNP sequence made in a laboratory. [The ANP, BNP and CNP guide](/learn/natriuretic-peptides/anp-vs-bnp-vs-cnp) compares the family it belongs to, and [the ANP guide](/learn/natriuretic-peptides/what-is-anp) explains the first member. The trial sits at the end of a longer story. Nesiritide was approved in the United States for early relief of dyspnoea in acute heart failure. Earlier meta-analyses, studies that pool earlier results, had raised questions about kidney harm and death. The paper gives this as the background for the trial. ![A tossed coin above simple blindfolded figures splitting into two equal groups, labelled Chance, Treatment group and Placebo group.](/assets/content/edu-randomised-double-blind-trial.png) ASCEND-HF was randomised and double-blind: chance put each of 7,141 patients into the nesiritide or placebo group, and neither patients nor doctors knew who was in which. Source: O'Connor et al., NEJM, 2011. ## What were the two co-primary endpoints of ASCEND-HF? The trial had two main questions, called co-primary endpoints. A co-primary endpoint is a main question the trial must answer. The first was the change in dyspnoea, or breathlessness, at 6 and 24 hours. Patients rated it on a 7-point Likert scale, picking one of seven answers from much worse to much better. The second was a composite: a return to hospital for heart failure, or death from any cause, within 30 days. A composite counts two kinds of event as one outcome. Choosing endpoints in advance keeps a trial honest, a little like calling a shot before taking it. The authors set a significance bar for the dyspnoea question before they saw the data, and that bar decides how the result is read. ## Did nesiritide meet the dyspnoea endpoint in ASCEND-HF? No. Slightly more patients on nesiritide said their breathing was markedly or moderately better. At 6 hours it was 44.5% against 42.1% on placebo (P = 0.03). At 24 hours it was 68.2% against 66.1% (P = 0.007). But the trial had set a strict bar in advance. To count as significant, P had to be 0.005 or less at both times, or 0.0025 or less at either one. That bar was not met. The authors describe the effect on dyspnoea as small and not significant when nesiritide was used with other therapies. A P value describes how incompatible the data are with a stated statistical model. It does not give the probability that an effect is real, and it does not measure how big the effect is. Here, the reported P values did not pass the stricter bar set before the trial results were known. In raw numbers, the gap was 2.4 percentage points at 6 hours and 2.1 at 24 hours. The abstract does not judge whether a gap that size matters to a patient. ## What did ASCEND-HF find for death, rehospitalisation and the kidneys? Nesiritide was not linked to a rise or a fall in death and return to hospital. Within 30 days, 9.4% of patients on nesiritide were readmitted for heart failure or died, against 10.1% on placebo (difference -0.7 percentage points; 95% confidence interval -2.1 to 0.7; P = 0.31). Death from any cause at 30 days was 3.6% against 4.0%. Kidney function got worse in 31.4% against 29.5% (odds ratio 1.09; 95% CI 0.98 to 1.21; P = 0.11). Worse here meant a fall of more than 25% in estimated glomerular filtration rate, a measure of kidney filtering. Hypotension, meaning low blood pressure, was more frequent with nesiritide. A confidence interval is the range of differences that fit the data. Here it includes zero, so these data do not establish a difference in that outcome. This does not prove that the two treatments have identical effects. The authors conclude that nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. [The half-life guide](/learn/natriuretic-peptides/anp-half-life-and-clearance) covers how fast the body clears BNP. ## What did earlier nesiritide trials measure? Earlier trials asked shorter-term questions. They measured changes in pressure and symptoms over hours, not the same questions as ASCEND-HF. A 2003 review of the VMAC study reports changes at 3 hours in pulmonary capillary wedge pressure, a pressure reading taken in the lung's blood vessels that reflects pressure in the heart. The mean changes were -5.8, -3.8 and -2 mm Hg for nesiritide, nitroglycerin and placebo, respectively, with all patients on standard therapy. The review also reports patient-rated dyspnoea at 3 hours. These patients had acute decompensated heart failure. The results are not evidence about healthy people or other natriuretic peptides. Those hours-long measures differ from the 30-day outcomes of ASCEND-HF. A short-term change in pressure and a longer-term outcome are different questions, and a good result on the first does not decide the second. [The medicines page](/learn/natriuretic-peptides/carperitide-nesiritide-and-vosoritide) places nesiritide beside the other natriuretic peptide medicines. ## What did ASCEND-HF not show? ASCEND-HF did not show that nesiritide changes death or return to hospital at 30 days. Its dyspnoea result also missed the bar set in advance. The trial enrolled only patients in hospital with acute heart failure. So it says nothing about people with other conditions, about the body's own BNP, or about any other natriuretic peptide. This page draws on the published abstract and the registry record. The full paper was not opened for this page, so details beyond the abstract are not stated here. The registry lists the sponsor as the company that made the drug, and the paper's funding note says the same. A company-funded trial can still be well run, and this one used a placebo and a large sample. But funding is a fact a reader should know. ## Comparison ASCEND-HF outcomes as stated in the published abstract, nesiritide against placebo. The table records reported numbers and the abstract's statistical statements, not a judgment of the drug. | Outcome | Nesiritide | Placebo | Statistical statement | | --- | --- | --- | --- | | Dyspnoea markedly or moderately improved, 6 hours | 44.5% | 42.1% | P = 0.03; the pre-specified bar was not met | | Dyspnoea markedly or moderately improved, 24 hours | 68.2% | 66.1% | P = 0.007; the pre-specified bar was not met | | Heart-failure rehospitalisation or death, 30 days | 9.4% | 10.1% | Difference -0.7 points; 95% CI -2.1 to 0.7; P = 0.31 | | Death from any cause, 30 days | 3.6% | 4.0% | Difference -0.4 points; 95% CI -1.3 to 0.5 | | Worsening kidney function | 31.4% | 29.5% | Odds ratio 1.09; 95% CI 0.98 to 1.21; P = 0.11 | ## Frequently asked questions ### How many patients were in ASCEND-HF? ASCEND-HF randomised 7,141 patients in hospital with acute heart failure to nesiritide or placebo. The registry also lists the enrolment as 7,141. ### Did nesiritide worsen kidney function in ASCEND-HF? The trial found no significant difference. Kidney function got worse in 31.4% of patients on nesiritide and 29.5% on placebo (odds ratio 1.09; 95% CI 0.98 to 1.21; P = 0.11). The authors write that nesiritide was not associated with a worsening of kidney function. ### Is nesiritide still sold in the United States? The FDA's [Drugs@FDA record](https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020920) lists the Natrecor product as discontinued. It also records a Federal Register determination that the product was not discontinued or withdrawn for safety or effectiveness reasons. ### What does a P value of 0.03 mean here? The reported P value of 0.03 did not clear the trial's pre-set bar. That bar was P of 0.005 or less at both time points, or 0.0025 or less at either one. A P value also does not give the probability that a result arose from chance alone. ## Citations - O'Connor CM, Starling RC, Hernandez AF, et al.. New England Journal of Medicine. 2011;365(1):32-43. DOI: 10.1056/NEJMoa1100171 - Wasserstein RL, Lazar NA.. The American Statistician. 2016;70(2):129-133. DOI: 10.1080/00031305.2016.1154108 - Keating GM, Goa KL.. Drugs. 2003;63(1):47-70. DOI: 10.2165/00003495-200363010-00004 --- Canonical page: https://www.formlaboratories.com/learn/natriuretic-peptides/ascend-hf-nesiritide-trial Form Laboratories - Perth-based research-use-only peptide supplier, shipping Australia-wide. - Site guide for agents: https://www.formlaboratories.com/llms.txt - Sitemap: https://www.formlaboratories.com/sitemap.xml - Full catalogue: https://www.formlaboratories.com/shop - Contact: hello@formlaboratories.com All materials are supplied for laboratory research use only - not for human or veterinary use, and nothing on this site is medical advice.