Proton Pump Inhibitors and Risk of Community-acquired Pneumonia

NCT02555852 | Completed

• 1 other identifier: CNODES_DEMO-2
• Study Type: observational
• Target: 4,238,504
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine whether proton pump inhibitors (PPIs), a medication used to treat gastric conditions, increase the risk of hospitalization for community-acquired pneumonia (HCAP). The investigators will carry out separate population-based cohort studies using administrative health databases in eight jurisdictions in Canada, the US, and the UK. Cohort entry will be defined by the initiation of an oral non-steroidal anti-inflammatory drug, with follow-up until hospitalization for pneumonia or end of follow-up (6 months). The results from the separate sites will be combined using a statistical approach called meta-analysis to provide an overall assessment of the risk of HCAP with PPIs.

Conditions

Gastroesophageal Reflux Disease (GERD); Community-acquired Pneumonia

Keywords

Proton Pump Inhibitors; Pneumonia; NSAIDs; Histamine H2 Antagonists; Drug safety

Outcome Measures

Primary Outcomes (1)

• Hospitalization for Community-Acquired Pneumonia (HCAP)

  HCAP during the 6 months following cohort entry Patients with HCAP with any of the following diagnostic codes: ICD-9: 487.0, 487.1, 487.0, 487.1, 487.0, 480.9, 481.x, 482.2, 482.0, 482.1, 482.30, 482.31, 482.32, 482.39, 482.40, 482.41, 482.42, 482.49, 482.81, 482.82, 482.83, 482.89, 482.9, 483.0, 484.7, 484.8, 485.X, 481.X, 486.X ; ICD-10: J10.0, J11.0, J11.1, J12.9, J13, J14, J15.X, J16.8, J17.0, J17.2, J17.3, J17.8, J18.0, J18.1, J18.8, J18.9.

  Patients will be followed from the date of study cohort entry until HCAP, censoring, or for up to 6 months.

Study Arms (3)

Users of PPIs

Exposure to proton pump inhibitors (PPIs) will be defined as a prescription for a PPI (esomeprazole, omeprazole, pantoprazole, lansoprazole, rabeprazole, and combinations) on the same day as the cohort entry defining prescription for an NSAID.

Drug: esomeprazole; Drug: omeprazole; Drug: pantoprazole; Drug: lansoprazole; Drug: rabeprazole

Users of H2RAs

Exposure to histamine-2 receptor antagonists (H2RAs) will be defined as a prescription for a H2RA (cimetidine, ranitidine, famotidine, nizatidine, niperotidine, roxatidine, ranitidine bismuth citrate, lafutidine, cimetidine combinations, and famotidine combinations) on the same day as the cohort entry defining prescription for an NSAID.

Drug: cimetidine; Drug: ranitidine; Drug: famotidine; Drug: nizatidine; Drug: niperotidine; Drug: roxatidine; Drug: ranitidine bismuth citrate; Drug: lafutidine; Drug: cimetidine combinations; Drug: famotidine combinations

Unexposed group (Reference)

Patients that are considered to be unexposed will be defined as patients not prescribed a PPI or H2RA on the same day as the cohort entry defining prescription for an NSAID.

Interventions

esomeprazole DRUG

Exposure to esomeprazole (ATC A02BC05, B01AC56, M01AE52, A02BD06) will be defined as a prescription for esomeprazole on the same day as a ≥ 30 day NSAID prescription.

Also known as: Proton pump inhibitor

Users of PPIs

omeprazole DRUG

Exposure to omeprazole (ATC A02BC01, A02BD01) will be defined as a prescription for omeprazole on the same day as a ≥ 30 day NSAID prescription.

Also known as: Proton pump inhibitor

Users of PPIs

pantoprazole DRUG

Exposure to pantoprazole (ATC A02BC02, A02BD04) will be defined as a prescription for pantoprazole on the same day as a ≥ 30 day NSAID prescription.

Also known as: Proton pump inhibitor

Users of PPIs

lansoprazole DRUG

Exposure to lansoprazole (ATC A02BC03, A02BD07, A02BD03, A02BD02) will be defined as a prescription for lansoprazole on the same day as a ≥ 30 day NSAID prescription.

Also known as: Proton pump inhibitor

Users of PPIs

rabeprazole DRUG

Exposure to rabeprazole (ATC A02BC04) will be defined as a prescription for rabeprazole on the same day as a ≥ 30 day NSAID prescription.

Also known as: Proton pump inhibitor

Users of PPIs

cimetidine DRUG

Exposure to cimetidine (ATC A02BA01) will be defined as a prescription for cimetidine on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

ranitidine DRUG

Exposure to ranitidine (A02BA02) will be defined as a prescription for ranitidine on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

famotidine DRUG

Exposure to famotidine (A02BA03) will be defined as a prescription for famotidine on the same day as a ≥30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

nizatidine DRUG

Exposure to nizatidine (A02BA04) will be defined as a prescription for nizatidine on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

niperotidine DRUG

Exposure to niperotidine (A02BA05) will be defined as a prescription for niperotidine on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

roxatidine DRUG

Exposure to roxatidine (A02BA06) will be defined as a prescription for roxatidine on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

ranitidine bismuth citrate DRUG

Exposure to ranitidine bismuth citrate (A02BA07) will be defined as a prescription for ranitidine bismuth citrate on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

lafutidine DRUG

Exposure to lafutidine (A02BA08) will be defined as a prescription for lafutidine on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

cimetidine combinations DRUG

Exposure to cimetidine combinations (A02BA51) will be defined as a prescription for cimetidine combinations on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

famotidine combinations DRUG

Exposure to famotidine combinations (A02BA53) will be defined as a prescription for famotidine combinations on the same day as a ≥ 30 day NSAID prescription.

Also known as: histamine-2 receptor antagonist

Users of H2RAs

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In each jurisdiction, the investigators will assemble a study cohort that includes all patients with a new prescription for an oral NSAID between January 1, 1997 and March 31, 2010. The date of study cohort entry is defined by the prescription date of the newly-prescribed NSAID.

You may qualify if:

• Patients with a first oral NSAID prescription
• Patients at least 40 years of age (except Alberta, Ontario, and Nova Scotia, where patients will be at least 66 years of age)
• Patients with at least 1 year of history in the database.

You may not qualify if:

• Patients aged \< 40 years at cohort entry (or \< 66 in Alberta, Ontario, and Nova Scotia)
• Received a prescription for a PPI, a H2RA, or a NSAID (any route of administration) in the 6 months prior to cohort entry
• Had an HCAP (ICD-9-CM code (in any field): 480.x-487.x; ICD-10-CA code: J10.0 - J18.9) or an extended emergency room visit for community-acquired pneumonia in the year prior to cohort entry (where available)
• Hospitalized at the time of cohort entry
• Received a prescription for medications used for the treatment of tuberculosis (ATC Code J04A) (where available)
• Had a history of cancer (other than non-melanoma skin cancer) in the year prior to cohort entry
• Hospitalized \>3 days within the 30 days before cohort entry
• Had \<1 year of continuous observation time in the database prior to cohort entry

Sponsors & Collaborators

• Canadian Network for Observational Drug Effect Studies, CNODES: lead
• Drug Safety and Effectiveness Network, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Lady Davis Institute for Medical Research, Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Related Publications (1)

• Filion KB, Chateau D, Targownik LE, Gershon A, Durand M, Tamim H, Teare GF, Ravani P, Ernst P, Dormuth CR; CNODES Investigators. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014 Apr;63(4):552-8. doi: 10.1136/gutjnl-2013-304738. Epub 2013 Jul 15.

  PMID: 23856153 RESULT

Related Links

• This organization's website describing general functions, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Gastroesophageal Reflux; Community-Acquired Pneumonia; Pneumonia

Interventions

Esomeprazole; Proton Pump Inhibitors; Omeprazole; Pantoprazole; Lansoprazole; Rabeprazole; Cimetidine; Histamine H2 Antagonists; Ranitidine; Famotidine; Nizatidine; niperotidine; roxatidine acetate; ranitidine bismuth citrate; lafutidine

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Community-Acquired Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Guanidines; Amidines; Imidazoles; Azoles; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Furans; Thiazoles

Study Officials

• Kristian Filion, PhD

  Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: September 22, 2015
• Study Start: September 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: September 22, 2015

Record last verified: 2015-09

Locations

CA (1)