Evidence map›Paper›PMID 25240705›Full record

Trial reportBMC cardiovascular disorders2014

Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials.

Helen M Colhoun, Jennifer G Robinson, Michel Farnier, Bertrand Cariou, Dirk Blom, Dean J Kereiakes, Christelle Lorenzato, Robert Pordy, Umesh Chaudhari

2 registry-linked trialsOpen access · goldFull text readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in BMC cardiovascular disorders, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
11.1field-weighted citation impact, top 1% of its field
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.

NCT01644175 phase3completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

TypeinterventionalSponsorSanofiRan2012 to 2014Enrolled316ConditionsHypercholesterolemiaArmsPlacebo (for alirocumab), Alirocumab, Lipid-Modifying Therapy (LMT)
NCT01644188 phase3completednot on this map

A Randomized, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 Versus Ezetimibe in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Statin Therapy

TypeinterventionalSponsorSanofiRan2012 to 2015Enrolled720ConditionsHypercholesterolemiaArmsAlirocumab, Placebo (for alirocumab), Ezetimibe, Placebo (for ezetimibe), Lipid Modifying Therapy (LMT)
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  13. Review
  14. Lipid Testing and Statin Dosing After Acute Myocardial Infarction.Journal of the American Heart Association · 2018
    Observational
  15. PCSK9 Inhibitors Show Value for Patients and the US Health Care System.Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research · 2017
    Article
  16. Article
  17. Review
  18. PCSK9 inhibitors in the prevention of cardiovascular disease.Journal of thrombosis and thrombolysis · 2016
    Review
  19. Review
  20. Targeting PCSK9 for therapeutic gains.Current atherosclerosis reports · 2015
    Review
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

9 authors at 9 institutions in 4 countries.

Helen M ColhounUniversity of Dundee, Dundee, Scotland DD2 4BF, UK. h.colhoun@dundee.ac.uk.
Jennifer G Robinson
Michel Farnier
Bertrand Cariou
Dirk Blom
Dean J Kereiakes
Christelle Lorenzato
Robert Pordy
Umesh Chaudhari
Center Point · USCentre Hospitalier Universitaire de Nantes · FRChrist Hospital · USRegeneron (United States) · USSanofi (France) · FRSanofi (United States) · USUniversity of Cape Town · ZAUniversity of Dundee · GBUniversity of Iowa · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events. METHODS/

designThe COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector). DISCUSSION: In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response. TRIAL REGISTRATIONS COMBO I: NCT01644175 ( NCT01644175). COMBO II: NCT01644188 ( NCT01644188).

Indexed as

Research DesignAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkersCardiovascular DiseasesCholesterol, LDLClinical ProtocolsDouble-Blind MethodDrug Therapy, CombinationHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypercholesterolemiaMaximum Tolerated DoseProprotein Convertase 9Proprotein ConvertasesRisk AssessmentalirocumabAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkersCholesterol, LDLHydroxymethylglutaryl-CoA Reductase InhibitorsPCSK9 protein, humanProprotein Convertase 9Proprotein ConvertasesSerine EndopeptidasesSerine Proteinase Inhibitors

Identifiers

PMID25240705
PMCPMC4190302
OpenAlexW1968507301

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

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.