Hydrochlorothiazide and Risk of Skin Cancer

NCT04334824 | Completed

• 1 other identifier: Q19-05
• Study Type: observational
• Target: 2,953,748
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether the use of hydrochlorothiazide is associated with an increased risk of skin cancer compared with the use of angiotensin-converting enzyme (ACE) inhibitors. More specifically, the investigators will assess the risk of non-melanoma and melanoma skin cancer. The investigators hypothesize that the use of hydrochlorothiazide is associated with an increased risk of skin cancer compared with ACE inhibitors. The investigators will carry out separate population-based cohort studies using administrative health databases from seven Canadian provinces and the United States. The study cohort will be defined by the initiation of hydrochlorothiazide or an ACE inhibitor, with follow-up until an incident diagnosis of non-melanoma or melanoma skin cancer. The results from the separate sites will be combined to provide an overall assessment of the risk of non-melanoma and melanoma skin cancer in users of hydrochlorothiazide.

Conditions

Non-melanoma Skin Cancer; Melanoma; Hypertension

Keywords

Non-melanoma Skin Cancer; Melanoma; Hydrochlorothiazide; Hypertension

Outcome Measures

Primary Outcomes (2)

• Non-melanoma skin cancer

  Incident non-melanoma skin cancer events will be identified using either cancer registry information (where available), or defined using an algorithm adapted from Chan et al., 2016. An event will be defined by the presence of a diagnosis code for non-melanoma skin cancer (ICD-9: 173.x; ICD-10: C44.x) plus a procedure code in hospital or physician claims data.

  Patients will be followed starting 366 days after study cohort entry until an incident diagnosis of non-melanoma skin cancer, censoring or for up to 275 months, whichever occurs first.

• Melanoma skin cancer

  Incident melanoma skin cancer events will be identified using either cancer registry information (where available), or defined using an algorithm. An event will be defined by the presence of a diagnosis code for malignant melanoma (ICD-9: 172.x; ICD-10: C43.x) plus a procedure code in hospital or physician claims data.

  Patients will be followed starting 366 days after study cohort entry until an incident diagnosis of melanoma skin cancer, censoring or for up to 275 months, whichever occurs first.

Study Arms (2)

Hydrochlorothiazide

Patients who received a new prescription for hydrochlorothiazide (alone or in combination with non-ACE inhibitor antihypertensive drugs) at cohort entry, and did not have a previous prescription for any antihypertensive drug any time before cohort entry.

Drug: Hydrochlorothiazide

Angiotensin-converting enzyme (ACE) inhibitors

Patients who received a new prescription for an ACE inhibitor (alone or in combination with non-hydrochlorothiazide antihypertensive drugs) at cohort entry, and did not have a previous prescription for any antihypertensive drug any time before cohort entry.

Drug: Angiotensin-converting enzyme (ACE) inhibitors

Interventions

Hydrochlorothiazide DRUG

Exposure to hydrochlorothiazide will be defined as a prescription for hydrochlorothiazide alone or in combination with non-ACE inhibitor antihypertensive drugs at cohort entry date.

Also known as: ATC C03AA03

Hydrochlorothiazide

Angiotensin-converting enzyme (ACE) inhibitors DRUG

Exposure to ACE inhibitors will be defined as a prescription for an ACE inhibitor alone or in combination with non-hydrochlorothiazide antihypertensive drugs at cohort entry date.

Also known as: ATC C09A, C09B

Angiotensin-converting enzyme (ACE) inhibitors

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 aged 40 years or older newly-treated with hydrochlorothiazide or an ACE inhibitor between April 1, 1995 and March 31, 2018 (or the latest date of data availability at each site). The date of study cohort entry will be defined by the dispensation date of the newly prescribed hydrochlorothiazide or ACE inhibitor.

You may qualify if:

• Patients aged 40 years or older (or 66 years or older in Alberta, Nova Scotia and Ontario) newly-treated with hydrochlorothiazide or an ACE inhibitor between April 1, 1995 and March 31, 2018 (or the latest date of data availability at each site)

You may not qualify if:

• Patients with less than one year of health coverage before cohort entry
• Patients with a previous prescription of any antihypertensive drug at any time before cohort entry
• Patients with a diagnosis of any type of skin cancer (non-melanoma and melanoma) at any time before cohort entry
• Patients with a diagnosis of HIV at any time before cohort entry
• Patients with a history of solid organ transplant at any time before cohort entry
• Patients with less than one year of follow-up after 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)

Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Related Publications (2)

• Chan AW, Fung K, Tran JM, Kitchen J, Austin PC, Weinstock MA, Rochon PA. Application of Recursive Partitioning to Derive and Validate a Claims-Based Algorithm for Identifying Keratinocyte Carcinoma (Nonmelanoma Skin Cancer). JAMA Dermatol. 2016 Oct 1;152(10):1122-1127. doi: 10.1001/jamadermatol.2016.2609.

  PMID: 27533718 BACKGROUND

• Azoulay L, St-Jean A, Dahl M, Quail J, Aibibula W, Brophy JM, Chan AW, Bresee L, Carney G, Eltonsy S, Tamim H, Paterson JM, Platt RW; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study. J Am Acad Dermatol. 2023 Aug;89(2):243-253. doi: 10.1016/j.jaad.2023.04.035. Epub 2023 Apr 25.

  PMID: 37105517 BACKGROUND

Related Links

• This is the website describing the general functions of the organization, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Melanoma; Hypertension

Interventions

Hydrochlorothiazide; Angiotensin-Converting Enzyme Inhibitors

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Laurent Azoulay, PhD

  Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: May 27, 2019
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: September 19, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)