Evidence map›Paper›PMID 27747305›Full record

ArticleJACC. Basic to translational science2016

Detection and Management of Geographic Disparities in the TOPCAT Trial: Lessons Learned and Derivative Recommendations.

Michael R Bristow, Jorge Silva Enciso, Bernard J Gersh, Christine Grady, Madeline Murguia Rice, Steven Singh, George Sopko, Robin Boineau, Yves Rosenberg, Barry H Greenberg

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Basic to translational science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Highlights in heart failure.ESC heart failure · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Michael R BristowCardiovascular Institute, University of Colorado, Boulder and Aurora, CO.
Jorge Silva EncisoUC San Diego Medical Center, La Jolla, CA.
Bernard J GershMayo Clinic, Rochester, MN.
Christine GradyDepartment of Bioethics, National Institutes of Health Clinical Center, Bethesda, MD.
Madeline Murguia RiceGeorge Washington University Biostatistics Center, Washington, DC.
Steven SinghWashington VA Medical Center, Washington, DC.
George SopkoDivision of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD.
Robin BoineauOffice of Clinical and Regulatory Affairs, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD.
Yves RosenbergDivision of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD.
Barry H GreenbergUC San Diego Medical Center, La Jolla, CA.

Funding

ZOPOLRESTAT PHARMACOKINETICS IN DIABETICS WITH VARYING RENAL FUNCTIONM01RR000051 · NCRR · UNIVERSITY OF COLORADO DENVER · PI ALBERT, RICHARD K · 1985 to 2008
$52.6M
Genetic-Adrenergic Interactions in Myocardial FailureR01HL048013 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BRISTOW, MICHAEL R. · 1993 to 2007
$4.5M
Dynamic Expression Profiling in the Intact Human HeartR01HL071118 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BRISTOW, MICHAEL R. · 2002 to 2003
$304k
ALDOSTERONE ANTAGONISTS FOR THE TREATMENT OF HEART FAILURE WITH PRESER-N01HC45207N01HC045207 · HC · NEW ENGLAND RESEARCH INSTITUTES. INC · PI MCKINLAY, SONJA M · 2004 to 2006
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NCRR NIH HHS M01 RR000051NHLBI NIH HHS HHSN268200425207CNHLBI NIH HHS N01 HC045207NHLBI NIH HHS R01 HL048013NHLBI NIH HHS R01 HL071118
6 · The paper itself

Abstract

TOPCAT was a multinational clinical trial of 3,445 heart failure with preserved ejection fraction (HFpEF) patients that enrolled in 233 sites in six countries in North America, Eastern Europe and South America. Patients with a heart failure hospitalization in the last 12 months or an elevated B-type natriuretic peptide (BNP) were randomized to the mineralocorticoid receptor antagonist spironolactone vs. placebo. Sites in Russia and the Republic of Georgia provided the majority of early enrollment, primarily based on the hospitalization criterion since BNP levels were initially unavailable there. With the emergence of country-specific aggregate event rate data indicating lower rates in Eastern Europe and differences in patient characteristics there, the DSMB recommended relatively increasing enrollment in North America plus other corrective measures. Although final enrollment reflected the increased contribution from North America, a plurality of the final cohort came from Russia and Georgia (49% vs. 43% in North America). BNP measurements from Russia and Georgia available later in the trial suggested no or a mild level of heart failure consistent with low event rates. The primary results showed no significant spironolactone treatment effect overall (primary endpoint hazard ratio 0.89 (0.77, 1.04)), with a significant hazard ratio in North and South America (0.82 (0.69, 0.98), p =0.026) but not in Russia and Georgia (1.10 (0.79, 1.51), interaction p = 0.12). This report describes the DSMB's detection and management recommendations for regional differences in patient characteristics in TOPCAT, and suggests methods of surveillance and corrective actions that may be useful for future trials.

Identifiers

PMID27747305
PMCPMC5065247

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.