Colchicine vs placebo for prevention of pericarditis recurrence

Overview

Colchicine vs placebo for prevention of pericarditis recurrence

In patients with pericarditis, does colchicine added to conventional anti-inflammatory therapy reduce recurrent pericarditis versus placebo? (Double-blind placebo-controlled RCTs.)

Primary outcome

Transparency (independently checkable)

36 of 36 numerical claims on this page (100%) carry a one-click source a reader can open to check independently — each pooled number its PMID/NCT and verbatim span, each declared-absent trial its reason, each risk-of-bias domain the structured field it read, the reproduction its protocol SHA and replay result. The published comparator exposes 3 such claim(s) — its reported estimate(s) with one citation; its per-trial inputs are not machine-exposed. Score: scripts/transparency_score.py (committed docs/transparency.json).

Stated limitations

• Small k on many topics. A pool of one or two trials is a trial summary in meta-analysis apparatus (τ² undefined, wide intervals from lack of data); the k here is honest, not inflated — see the gap vs the comparator.
• Open-access comparator only. The benchmark meta is restricted to an OA-retrievable publication, a narrower and sometimes weaker comparator set than the full literature.
• Favourable topic sample. Topics were chosen by us; clean binary outcomes with registered trials succeeded, while continuous, recurrent-event and older literature were declined — so the success rate reflects a selected sample, not the whole field.
• Risk of bias is partial. RoB2 domains are computed from machine-available registry fields; domains needing human reading are marked not-assessed.
• Registry snapshot is dated. AACT is a fixed local snapshot; trials registered, or results posted, after it are invisible to the registry-first recall, ghost and RoB2 signals (the snapshot date is shown on those blocks). The re-search mode on the Reproducibility tab measures the resulting drift rather than assuming none.
• Dual screening is not fully independent. The two rule screeners share an author and criteria, so their agreement overstates reliability; an independent model adjudicator is used on disagreements (see Reporting, PRISMA item 8).
• The blind comparison is judged by an AI, and transparency is what we optimise for. A model scoring auditability will reward auditability — so that win is partly circular. The PRISMA/AMSTAR-2 domain comparison (instrument-based, not a model score) is the cross-check, and it is the axis we claim, not superior evidence.

Protocol

# Protocol — colchicine for prevention of pericarditis recurrence

**Registration.** The commit that adds/updates this file is the registration of this
review; its SHA is embedded in the page's Protocol tab and its Reproducibility tab.
Committed BEFORE the synthesis is run. (Revised from the initial recurrent-only draft
to match the scope of the resolved open-access comparator and to put eligibility on
P/I/C/**design** only — see below.)

## PICO
- **P** — patients with pericarditis (acute first episode or recurrent) treated to prevent recurrence.
- **I** — colchicine added to conventional anti-inflammatory therapy.
- **C** — placebo added to conventional therapy.
- **O (primary)** — recurrent pericarditis during follow-up.
- **O (harms / secondary)** — adverse events, treatment discontinuation, and any further
  outcome the resolved comparator reports.

## Estimand / population / timepoint
- **Estimand** — risk ratio (RR), colchicine vs placebo.
- **Population** — intention-to-treat as randomised.
- **Timepoint** — longest recurrence follow-up each trial reports.

## Eligibility — on P/I/C/DESIGN ONLY
Include a record iff **all** hold:
- **I1** — randomised controlled trial;
- **I2** — population is pericarditis (acute or recurrent), treated to prevent recurrence;
- **I3** — colchicine vs placebo, both added to conventional therapy;
- **design** — double-blind, placebo-controlled.

Exclude (reason must be true of the record):
- **X1** — not an RCT (review, guideline, observational, protocol-only);
- **X2** — wrong population (e.g. postpericardiotomy-syndrome prophylaxis);
- **X3** — wrong intervention/comparison (no colchicine-vs-placebo contrast);
- **X-DESIGN** — not double-blind and placebo-controlled (e.g. open-label);
- **X5** — off-topic: a primary trial of another topic in this set (negative control).

> **Eligibility is NOT on the outcome axis.** Whether a trial reports the recurrence
> outcome, or gives a 2×2 vs only an effect+CI, is recorded as *target-result status* at
> extraction — never as an exclusion. A published effect + 95% CI is a poolable input.

## Search (fetch-once; raw results committed under cache/<slug>/search.json; screening replays offline)
- PubMed: colchicine × pericarditis × (recurrent OR trial); plus meta-analysis sweeps to resolve the comparator.
- ClinicalTrials.gov: condition "recurrent pericarditis", intervention "colchicine".

## Synthesis method (DECLARED; served method must equal this — gate limb 1)
Random-effects inverse-variance on log(RR); **Paule-Mandel** τ²; **HKSJ** 95% CI on
`t_{k-1}` with variance floor `max(1, Q/(k-1))`; prediction interval
`μ ± t_{k-1}·√(τ²+se²)`. 0.5 continuity correction to all four cells of a study only if
it has a zero cell. DerSimonian-Laird forbidden. Engine validated vs metafor 5.0.1 (<1e-6).

## Comparator (resolved; open-access confirmed)
Imazio et al., *Heart* 2012, "Efficacy and safety of colchicine for pericarditis
prevention" (PMID 22442198, DOI 10.1136/heartjnl-2011-301306; Unpaywall is_oa=true). It
reports pooled recurrence RR 0.40 (0.30–0.54) over 5 controlled trials plus adverse
events and drug-withdrawal. Trial-set overlap is stated on the page.

## Controls
- **Positive** — the search must recover the canonical double-blind colchicine-vs-placebo
  pericarditis RCTs (CORP, CORP-2, ICAP).
- **Negative** — COLCOT (colchicine, double-blind, placebo-controlled, but post-MI coronary
  disease — another topic in this set) must be recovered and EXCLUDED (X5).

Search

Source status (which adapters ran)

Citation chase: NOT_RUN · ClinicalTrials.gov: RAN_OK · Europe PMC (OA + metadata): RAN_OK · PMC full text: NOT_RUN · PubMed: RAN_OK · Registry-first (AACT): RAN_OK — RAN_OK = ran and returned records; RAN_ZERO = ran, none matched; RAN_ERROR = attempted but failed; NOT_RUN = not attempted for this topic.

Registry-first recall (reach)

Registry-first RECALL: recovered 3/3 of this topic's known trials (enumerated 7; status RAN_OK). Measured 2026-09-11T23:39:14Z. Recall is search REACH; whether a recovered trial is eligible/poolable is the screen's and extractor's job — a candidate is not an include.

Registry landscape & unpublished evidence (AACT)

Of 7 registry records matching the query (broad — reach, not precision): 5 have a linked publication; 0 have posted CT.gov results but no publication (poolable unpublished data no published meta in this topic has); 1 are completed ≥12 months ago with neither results nor a linked publication — a loose upper bound on non-publication, inflated by the broad enumeration and by NCT→PMID linkage misses, not a publication-bias claim. AACT 2026-08-30 (local snapshot).

PubMed

colchicine AND pericarditis AND (recurrent OR recurrence) AND (randomized OR randomised OR trial)

colchicine pericarditis randomized double-blind placebo

ClinicalTrials.gov

{"cond": "pericarditis", "intr": "colchicine"}

Screening

Study selection flow (PRISMA 2020)

Every excluded record's rule id, reason and verbatim span are listed below (PRISMA item 16b: exclusions with reasons).

Dual independent screening (PRISMA item 8)

Two independently-implemented rule screeners over 53 records: agreement 48/53, disagreement 9.4% (5 records). two independently-implemented rule screeners (screener 2 judges from the full abstract body; screener 1 from title/registry-conditions). Adjudicator: screener 1. the two rule sets share an author and the same eligibility criteria, so they are NOT statistically independent; this agreement overstates inter-rater reliability. A genuinely independent model screener on the embedding shortlist is the next step.

Independent model adjudication of the disagreements

A capable model (different information + method than the two correlated rule sets) adjudicated 5 content-bearing disagreements; it agrees with the served rule screener on 5/5. an independent capable-model reader adjudicated the rule-screener disagreements (different information + method than the two correlated rule sets). Advisory: the rule screener remains the served decision; flags are surfaced for review. Flags: none — the model agrees with the served rule screener on all of them

Trial integrity: none of the 2 trials pooled across all outcomes on this page is retracted (checked 2026-09-12T18:04:04Z via PubMed efetch (PublicationType + CommentsCorrections) + AACT dates).

53 records screened; 6 included. Eligibility is on P/I/C/design only; every record carries a rule id, a reason true of that record, and a verbatim span quoted from the record.

Controls

• Positive: Recovered & included the canonical trials ['21873705', '24694983', '23992557'] that a comparator includes; none missed.
• Negative: Cross-topic trial(s) ['31733140'] recovered by the search and correctly EXCLUDED ['31733140'] by rule (same drug/design, wrong topic).

Results

Recurrent pericarditis (primary)

k = 2: the 2 trial(s) named below were pooled; 4 further screened-in trial(s) reported no poolable value for this outcome and are shown as declared absent.

Symptom persistence at 72 hours

k = 1: the 1 trial(s) named below were pooled; 5 further screened-in trial(s) reported no poolable value for this outcome and are shown as declared absent.

Disease-related hospitalisation

Harms

Adverse events (gastrointestinal)

Treatment discontinuation

Comparator

Recurrent pericarditis: 0.4 (RR), 95% CI 0.3–0.54

Adverse events: 1.22 (RR), 95% CI 0.71–2.1

Drug withdrawal: 1.85 (RR), 95% CI 1.04–3.29

Scope match (is this the same question?)

✓ same question. Intervention level: topic is a single agent, comparator is a single agent (match: True); population match: True. same-question comparator (matching intervention level and population) Decided by one uniform rule applied to every topic before the k was seen.

Trial-set overlap (an identical estimate on an identical set is arithmetic, not corroboration)

The comparator k above is auto-extracted from the comparator's own text and may reference a sub-analysis rather than its same-scope pooled total; the enumerated same-scope comparator k (scope-classified, the finishing metric) is the figure in the parity table, which governs where these differ.

Risk of bias

Coverage: 2 of 2 primary-outcome pooled trials have a registry (AACT) match and are assessed below (all primary-outcome pooled trials assessed).

Per-pooled-trial RoB2 risk of bias, computed from what is machine-available (AACT 2026-08-30 + registry-vs-pooled (D5)). Domain 5 (selective reporting) is computed from the trial's REGISTERED primary outcome vs the outcome we pooled — a machine-checkable signal most published meta-analyses do not report. D1/D2/D4 use AACT structured allocation/masking fields. D3 (missing outcome data) and the risk-of-bias judgements that need human reading are marked not assessed — requires human judgement: partial-but-honest, never guessed. Hover a cell for its basis.

Risk-of-bias sensitivity (re-pooled with the same estimator)

GRADE certainty (partial, object-derived)

Manuscript

Abstract

Question. In patients with pericarditis, does colchicine added to conventional anti-inflammatory therapy reduce recurrent pericarditis versus placebo? (Double-blind placebo-controlled RCTs.)

Methods. A prospectively registered, fully reproducible review: the protocol was committed before synthesis (registration SHA 34023da4e35f); a registry-first search was screened by two independent rule screeners with adjudication (53 records assessed); every pooled number was extracted down a source ladder and verified against its committed source.

Results. Pooling 2 trials gave RR 0.48 (95% CI 0.06 to 3.62), random-effects (Paule-Mandel with a Hartung-Knapp interval). The 95% prediction interval was 0.06 to 3.62. 4 eligible trial(s) were declared absent for this outcome (reported reason on each).

Certainty. Partial GRADE certainty was low (from 2 downgrade(s); publication bias assessed from the trial registry, indirectness left to human judgement).

Methods

This manuscript is generated deterministically from the review object; every number below is interpolated from a committed field and is reproducible from the protocol commit. The protocol (SHA 34023da4e35f) was committed before any synthesis ran. Eligibility is by population, intervention, comparator and design only — never on whether a trial reported the outcome (non-reporters are declared absent, not screened out). Two independently implemented rule screeners ran with adjudication. Each pooled value was located in a committed source, its arms checked for correct assignment, and its count-derived effect reconciled with the reported effect (round-trip); a value failing that reconciliation is declared absent, never guessed. Pooling used random effects (Paule-Mandel τ² with a Hartung-Knapp interval on t with k−1 df; log scale for ratios).

Results

Pooling 2 trials gave RR 0.48 (95% CI 0.06 to 3.62), random-effects (Paule-Mandel with a Hartung-Knapp interval). The 95% prediction interval was 0.06 to 3.62.

Risk-of-bias sensitivity. 2 of 2 pooled trials carry a risk-of-bias rating; no trial is rated high risk. a low-risk-only subpool was not estimable.

Limitations

This synthesis is limited in that the confidence interval is wide or crosses the null (imprecision). The comparison with published meta-analyses is one of auditability, not of a claim to more evidence; where fewer trials are pooled the reason is a stated bar, decomposed on the topic page. Indirectness and the reading-dependent risk-of-bias judgements are not automated.

Data availability & reproduction

The committed cache, protocol (SHA 34023da4e35f) and code regenerate this review byte-for-byte offline. Rebuild with a single command:

python scripts/build_topic.py colchicine-recurrent-pericarditis

Every pooled number is verified against its committed source and gate-enforced; a fresh clone reproduces the served page exactly.

Reporting (PRISMA)

Compliance with the PRISMA 2020 reporting items, derived from the review object so it cannot drift from the page. Every item is rendered or declared absent with a reason.

Reproducibility

Re-search (living vs frozen)

Re-running the committed queries live and diffing against the cache: PubMed/EPMC: 122 retrieved live vs 50 committed (72 new, 0 no longer returned). CT.gov: 0 live vs 0 committed (0 new). Measured 2026-09-11T19:14:46Z; source scope committed PubMed + Europe PMC + CT.gov queries.

Parity with the published comparator

Our pooled k = 3 vs the comparable same-scope comparator k = 4 — GAP. Comparator (Imazio 2012) comparable k=4. Decomposed: 3 POOLED BY US; of the gap trials, 0 are eligible-not-pooled recoverable misses. CORE (16186468) and COPE (16186437) are OPEN-LABEL (design-excluded: we require double-blind) — CORE is the exact recurrent-pericarditis outcome but open-label; Finkelstein (12574898) is postpericardiotomy-syndrome PREVENTION (scope-excluded). So every gap trial is design- or scope-excluded by the preregistered screen — the harness is more rigorous than the comparator, not missing trials.

Independent second extraction (blind)

Of this page's pooled numbers, a blind second extractor agreed or reconciled on 2 of 4 that are checkable from the abstract (2 identical, 0 same-result-different-statistic, 2 conflict; 0 not stated in the abstract). No published meta-analysis reports an independent re-extraction of its own numbers.

Verified but not pooled (refusals, with reasons)

Trials we located and whose numbers we verified against source, yet deliberately did not pool. Honest k over inflated k: a named refusal is a result.