Intravenous iron against placebo or usual care in heart failure with iron deficiency: six outcomes under four effect measures, pooled within three families and across none, with the two endpoints that carry no ordinary interval reported from single trials

In adults with heart failure and iron deficiency, what is the effect of intravenous iron restricted here to ferric carboxymaltose or ferric derisomaltose compared with placebo or usual care on recurrent hospitalisations for heart failure with and without cardiovascular death, on the time to a first such event, on death from any cause, on a hierarchical composite of death, hospitalisation and walk distance, and on exercise capacity itself -- with each of those questions answered separately?

In this section: Registration and administrative information (PROSPERO field set) · What this object claims to contain

Registration and administrative information (PROSPERO field set)

Table 1. Registration and administrative information (PROSPERO field set)
Review title	Intravenous iron against placebo or usual care in heart failure with iron deficiency: six outcomes under four effect measures, pooled within three families and across none, with the two endpoints that carry no ordinary interval reported from single trials
Review question (PICO)	In adults with heart failure and iron deficiency, what is the effect of intravenous iron restricted here to ferric carboxymaltose or ferric derisomaltose compared with placebo or usual care on recurrent hospitalisations for heart failure with and without cardiovascular death, on the time to a first such event, on death from any cause, on a hierarchical composite of death, hospitalisation and walk distance, and on exercise capacity itself -- with each of those questions answered separately?
Population	Adults with HFrEF and iron deficiency (ferritin <100 ng/mL, or 100-299 with TSAT <20%)
Intervention	Intravenous ferric carboxymaltose or ferric derisomaltose
Comparator	Placebo or standard of care
Background / rationale	Not recorded — this object holds no background field, and an introduction generated without one would be argument that no source in this review supports
Eligibility criteria	Eligibility turns on population, intervention, comparator, route and outcome. The population is adults with heart failure and iron deficiency. The intervention is intravenous iron as ferric carboxymaltose or ferric derisomaltose. The comparator is placebo OR usual care -- and the second half is load-bearing rather than generous: one contributing trial randomised against usual care, so a placebo-only criterion would exclude it, which is the defect this criterion was written to avoid. The outcome criterion is that the trial designates a CLINICAL-EVENT endpoint, or a registered functional primary that a regulator relies on. The word adjudicated is deliberately absent from this criterion, and the reason is not that adjudication is rare here: two contributing trials' staged sources state it plainly -- one abstract records masked adjudication of the outcomes, and one full text records an independent clinical endpoint committee adjudicating all hospitalisations and deaths. What cannot be shown is that every contributing trial's staged sources establish it, so a criterion demanding adjudication would be one this review could not show all its own members satisfy. An earlier version of this sentence said only one trial's sources state adjudication, which a later correction in this same object contradicted the moment it established the second -- a fix that created its own inconsistency by not sweeping back to the sentences that quantify over the fact it added. NO criterion refers to membership of a list.
Information sources	15 source layers, listed on the Extraction tab
Search strategy	The executed strings, datetimes, filters and hit counts are on the Search tab
Study selection process	A second independent screen was NOT run. No second independent screen was run for this topic. This is recorded as owed rather than described: the remedy is to RUN one, and writing a duplicate-screening sentence without one would be the defect this whole exercise exists to prevent.
Number of screeners	One. No second independent screen was run.
Data extraction items	Extracted per trial on this object: registry id; primary publication; year; design; arms; per-arm counts and the published effect; the randomised total, separately from the analysed denominator. Fields not listed here were not extracted.
Outcomes and prioritisation	Recurrent hospitalisations for heart failure together with cardiovascular death, as a rate ratio; Time to a first cardiovascular death or hospitalisation for heart failure, as a hazard ratio; Recurrent hospitalisations for heart failure alone, with no death component, as a rate ratio; Time to death from any cause, as a hazard ratio; A hierarchical composite of death, hospitalisations for heart failure and change in walk distance, as an unmatched win ratio; Change in six-minute walk distance at the primary timepoint, in metres
Risk of bias method	RoB 2, per result, five domains — see the risk-of-bias table below
Synthesis methods	Pooled under random-effects with the REML estimator. These methods were NOT prespecified before the search, and are not presented as though they were.
Subgroup analyses	Not recorded — this object records no subgroup-analysis field at all, so whether any were prespecified is UNKNOWN -- which is not the same as none having been
Meta-bias assessment	Not recorded — no funnel, Egger or Peters value is held on this object, so no meta-bias assessment is claimed
Certainty assessment	GRADE, recorded for 6 outcome(s) (GRADE). The ratings are on the Certainty tab.
Confidence level	95%
Funding	Not recorded — no funding statement is recorded for this review
Competing interests	Not recorded — no declaration is recorded
Built	2026-08-10
Schema	2

What this object claims to contain

Full build, with a stated boundary on the search and with a rediscovery test behind it rather than an assertion that a search ran. Every randomised trial the staged search record enumerates -- the trials this review contains, the trials the two prior syntheses name in their own lists, and the ongoing trials at or above the enrolment threshold that record applies -- is either contributing here, or in one screening log with the eligibility criterion it fails and the quantity it reports instead, or listed as eligible and not yet reporting. What is not claimed, and what an earlier version of this sentence did claim, is a disposition for every hit the class-keyed query returns: that query returns far more records than this object classifies, and the staged record scopes its own enumeration by size rather than silently. A reader who wants the unenumerated tail should read the query in that record and run it. There is exactly one source list, `screening.records`; `screening.excluded` is a view computed from it at build time, row for row, so it cannot say anything the records do not. What this statement does not claim is a systematic multi-database search: none was run, the limitation is recorded in the screening block, and some of the screened-out records are characterised from a prior synthesis's table rather than from the trials' own reports. How many is deliberately not asserted in this sentence: it is computed from the records at build time into the screening block, and each of those rows says on itself that it rests on that table. An earlier version typed a count here that was wrong by one against the object's own array, which is what a prose copy of a countable fact does.

In this section: Search — executed, source by source · Search record: search · PRISMA flow · ClinicalTrials.gov API v2 -- query 1, narrower, and it missed two included trials · ClinicalTrials.gov API v2 -- query 2, broader, full recall on the included set

Search — executed, source by source

Search record: search

executed_by — lane 1 (Claude, Anthropic family)

Databases: ClinicalTrials.gov API v2 -- QUERY 1, NARROWER, AND IT MISSED TWO INCLUDED TRIALS (<a href='https://clinicaltrials.gov/api/v2/studies (raw, curl)' rel='noopener'>query</a>), ClinicalTrials.gov API v2 -- QUERY 2, BROADER, FULL RECALL ON THE INCLUDED SET (<a href='https://clinicaltrials.gov/api/v2/studies (raw, curl)' rel='noopener'>query</a>)

PRISMA flow

Table 2. PRISMA flow
Stage	Records
identification	{'ctgov_query1': 16, 'ctgov_query2': 47, 'note': "Query 2 supersedes query 1 for coverage; both are recorded, because query 1's miss is a finding about search recall."}
eligibility ctgov	{'role_located': 43, 'topic_is_experimental_arm': 34, 'topic_is_comparator_arm': 6, 'topic_is_background': 3, 'not_assessable': 4}
included	{'in_this_object': 5, 'nct': ['NCT01453608', 'NCT02937454', 'NCT02642562', 'NCT03037931', 'NCT03036462']}
reconciliation	{'arithmetic': '47 identified = 34 experimental + 6 comparator + 3 background + 4 not_assessable; 43 of the 47 had a role located', 'reconciles': True, 'unscreened_remainder': 0, 'remainder_means': '34 trials place intravenous iron in the randomised experimental arm; 5 are in this object; the other 29 were ALL SCREENED on 2026-08-19 and the remainder is now 0. Dispositions: 13 excluded, 6 eligible but not poolable, 10 eligible with no results yet. The third state is kept because a trial nobody has looked at is not a trial that was assessed and rejected -- and neither is one that has not reported.'}

ClinicalTrials.gov API v2 -- query 1, narrower, and it missed two included trials

Query as executed:

query.cond="chronic heart failure"; query.intr="ferric carboxymaltose OR iron sucrose OR ferric derisomaltose OR iron isomaltoside"; filter.advanced=AREA[StudyType]INTERVENTIONAL; pageSize=100; countTotal=true

ClinicalTrials.gov API v2 -- query 2, broader, full recall on the included set

Query as executed:

query.cond="heart failure"; query.intr="ferric carboxymaltose OR iron sucrose OR ferric derisomaltose OR iron isomaltoside OR intravenous iron"; filter.advanced=AREA[StudyType]INTERVENTIONAL; pageSize=200; countTotal=true

In this section: FAIR-HF NCT00520780 · EFFECT-HF NCT01394562 · Toblli 2007 · FERRIC-HF 2008 · PRACTICE-ASIA-HF 2018 · Dhoot 2020 · IRON-CRT 2021 · Oral iron protein succinylate NCT03344523