Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions

NCT03387540 | Completed FDA Drug

• 1 other identifier: CIC1421-17-12
• Study Type: observational
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase.

Conditions

Myocarditis; Cardiac Complication

Keywords

Anti-PD-1; Anti-PD-L1; Anti CTLA-4; Immune checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

• Cardio-vascular toxicity of ICIs.

  Identification and report of the cardio-vascular toxicity of ICIs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT), Cardiac and vascular investigations (excl enzyme tests) (HLGT), Skeletal and cardiac muscle analyses (HLT). Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

  Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

Secondary Outcomes (6)

• Causality assessment of reported cardiovascular events according to the WHO system

  Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

• Description of the type of cardiotoxicity depending on the category of ICIs

  Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

• Description of the duration of treatment when the toxicity happens (role of cumulative dose)

  Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

• Description of the drug-drug interactions associated with adverse events

  Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

• Description of the pathologies (cancer) for which the incriminated drugs have been prescribed

  Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

Study Arms (1)

Myocarditis induced by Immune check point inhibitor

Case reported in the World Health Organization (WHO) of myocarditis of patient treated by ICI, with a chronology compatible with the drug toxicity

Drug: ICI

Interventions

ICI DRUG

Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Myocarditis induced by Immune check point inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients treated with an ICI for a cancer

You may qualify if:

• Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
• Adverse event reported were including the MedDRA terms: Cardiac and vascular investigations (excl enzyme tests) (HLGT), Vascular disorders (SOC), Skeletal and cardiac muscle analyses (HLT), Sudden death (PT), Sudden cardiac death (PT), Cardiac disorders (SOC), Cardiac arrhythmias (HLGT), Cardiac disorder signs and symptoms (HLGT), Cardiac neoplasms (HLGT), Cardiac valve disorders (HLGT), Congenital cardiac disorders (HLGT), Coronary artery disorders (HLGT), Endocardial disorders (HLGT), Heart failures (HLGT), Myocardial disorders (HLGT), Pericardial disorders (HLGT)
• Patients treated with ICIs included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

You may not qualify if:

• Chronology not compatible between the drug and the toxicity

Sponsors & Collaborators

• Groupe Hospitalier Pitie-Salpetriere: lead
• Institute of Cardiometabolism and Nutrition, France: collaborator
• Vanderbilt University: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.

Paris, 75013, France

Location

Related Publications (4)

• Dressler D, Potter H. Molecular mechanisms in genetic recombination. Annu Rev Biochem. 1982;51:727-61. doi: 10.1146/annurev.bi.51.070182.003455. No abstract available.

  PMID: 6287923 BACKGROUND

• Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018 Mar 10;391(10124):933. doi: 10.1016/S0140-6736(18)30533-6. No abstract available.

  PMID: 29536852 RESULT

• Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Reporting of immune checkpoint inhibitor-associated myocarditis - Authors' reply. Lancet. 2018 Aug 4;392(10145):384-385. doi: 10.1016/S0140-6736(18)31556-3. No abstract available.

  PMID: 30102170 RESULT

• Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano JP, Balko JM, Bonaca MP, Roden DM, Johnson DB, Moslehi JJ. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018 Dec;19(12):1579-1589. doi: 10.1016/S1470-2045(18)30608-9. Epub 2018 Nov 12.

  PMID: 30442497 RESULT

MeSH Terms

Conditions

Myocarditis

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Target Duration: 2 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle investigator

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: January 2, 2018
• Study Start: December 2, 2017
• Primary Completion: December 4, 2017
• Study Completion: December 31, 2017
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

FR (1)