Trials Sponsors Conditions Drugs Pricing

Conditions

Keywords

NortriptylineTricyclic antidepressantsOlder adultsSerious adverse eventsChronic kidney diseaseCohort studyGlomerular filtration rate

Outcome Measures

Primary Outcomes (1)

Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality.
30-day all-cause emergency department visit, all-cause hospitalization, and all-cause mortality will be combined into a composite measure. Only the first hospitalization or emergency department visit occurring after the cohort entry date will be considered.
Older adults exposed to high-dose (>10-150 mg/day) vs low-dose (10 mg/day) oral nortriptyline will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

Secondary Outcomes (7)

Number of participants with 30-day all-cause emergency department visit.
Older adults exposed to high-dose (>10-150 mg/day) vs low-dose (10 mg/day) oral nortriptyline will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.
Number of participants with 30-day all-cause hospitalization.
Older adults exposed to high-dose (>10-150 mg/day) vs low-dose (10 mg/day) oral nortriptyline will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.
Number of participants with 30-day all-cause mortality
Older adults exposed to high-dose (>10-150 mg/day) vs low-dose (10 mg/day) oral nortriptyline will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.
30-day composite outcome of a hospital encounter with fragility fracture, falls, hypotension, or syncope.
Older adults exposed to high-dose (>10-150 mg/day) vs low-dose (10 mg/day) oral nortriptyline will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.
30-day hospital encounter composite of atrial fibrillation/flutter, ventricular arrhythmia/sudden cardiac death, and other arrhythmia.

Study Arms (2)

Low dose nortriptyline (10 mg/day)

Residents of Ontario, aged 66 years or older with low kidney function (an eGFR \<45 mL/min per 1.73 m² but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for nortriptyline (low dose 10 mg/day) at an outpatient pharmacy under the Ontario Drug Benefit program from January 01, 2008, to December 01, 2025. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. If the investigators conduct the study in Alberta, the accrual period for Alberta will be determined.

Drug: Nortriptyline Hydrochloride

High dose nortriptyline (>10-150 mg/day)

Residents of Ontario, aged 66 years or older with low kidney function (an eGFR \<45 mL/min per 1.73 m² but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for nortriptyline (high dose \>10-150 mg/day) at an outpatient pharmacy under the Ontario Drug Benefit program from January 01, 2008, to December 01, 2025. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. If the investigators conduct the study in Alberta, the accrual period for Alberta will be determined.

Drug: Nortriptyline Hydrochloride

Interventions

Nortriptyline HydrochlorideDrug

The primary exposure of interest will be oral nortriptyline at a dose of \>10-150 mg/day. For the primary comparison, oral nortriptyline at 10 mg/day will serve as the referent group to reduce confounding by indication.

Also known as: Nortriptyline, Aventyl, Pamelor, Tricyclic antidepressant

High dose nortriptyline (>10-150 mg/day)Low dose nortriptyline (10 mg/day)

Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.

Eligibility Criteria

Age66 Years+

Sexall

Healthy VolunteersNo

Age GroupsOlder Adult (65+)

Sampling MethodNon-Probability Sample

Study Population

Adults aged 66 years or older with low kidney function (eGFR \<45 mL/min per 1.73 m2 but not receiving dialysis or having a history of kidney transplantation) who have filled a new outpatient prescription of oral nortriptyline between 2008 and 2025 in Ontario.

You may qualify if:

The cohort will include all older adults (≥66 years) with an eGFR \<45 mL/min per 1.73 m2 (not receiving dialysis or having a history of kidney transplantation) who received a new outpatient prescription for oral nortriptyline between January 1, 2008, and December 1, 2025.

Sponsors & Collaborators

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Otherlead

Related Publications (3)

Koiso K, Akaza H, Kikuchi K, Aoyagi K, Ohba S, Miyazaki M, Ito M, Sueyoshi T, Matsushima H, Kamimura H, Watanabe T, Higuchi S. Pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment: effects of alpha 1-acid glycoprotein. J Clin Pharmacol. 1996 Nov;36(11):1029-38. doi: 10.1177/009127009603601107.
PMID: 8973992BACKGROUND
Abdullah SS, Rostamzadeh N, Muanda FT, McArthur E, Weir MA, Sontrop JM, Kim RB, Kamran S, Garg AX. High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol. Can J Kidney Health Dis. 2024 Jan 6;11:20543581231221891. doi: 10.1177/20543581231221891. eCollection 2024.
PMID: 38186562BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

NortriptylineAntidepressive Agents, Tricyclic

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Enrollment

5,000 participants (actual enrollment reported by the registry).

Study Design

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

Study Record Dates

First Submitted

April 7, 2026

First Posted

April 14, 2026

Study Start

January 1, 2008

Actual (reported)

You may not qualify if:

Individuals with missing administrative database number, missing or invalid age (\<0 or \>105 years), missing or invalid sex, death on or before the index date, non-Ontario resident (for Ontario data), or non-Alberta residents (for Alberta data).
Individuals less than 66 years of age on the index date.
Those with evidence of any study drug prescription 180 days before the index date (to restrict to new users only).
Individuals with more than one study drug prescription on the index date, as this complicates the ability to ascertain the prescribed dose accurately.
Evidence of clinically non-meaningful nortriptyline doses (doses that are either too low or too high). The recommended nortriptyline dose range is 10 to 150 mg per day.
Evidence of other tricyclic antidepressants in the previous 180 days (including index date).
Individuals with end-stage renal disease, chronic dialysis, or a kidney transplant prior to the index date.
Evidence of a hospital discharge or emergency department visit in the two days prior to or on the index date to ensure a new outpatient prescription.
Individuals with no serum creatinine lab value in the 0-365 days prior to the index date.
Individuals with unstable baseline kidney function:
If the most recent serum creatinine test prior to the index date was an inpatient test \[ER or hospitalization\] \<refer to this as test date 1\>, and there is not at least one outpatient serum creatinine in the year before test date 1, OR If the most recent prior serum creatinine test prior to the index date was an inpatient test \[ER or hospitalization\] \<refer to this as test date 1\>, and while there is at least 'outpatient' serum creatinine test in the year before \<test date 1\>, the most recent outpatient test prior to \<test date 1\> differs by an eGFR of 10 mL/min/1.73 m2 or more from the value on \<test date 1\>.
In Ontario, it has been shown that outpatient serum creatinine measurements in the province, conducted on a single occasion, indicate stable values.
The investigators restrict to the first prescription in individuals with more than one eligible prescription. The date of this prescription will be the index date (the date from which outcomes start being assessed).

Nortriptyline and the Risk of Serious Adverse Events

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

Study Start

Primary Completion

First Submitted

First Posted

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (7)

Study Arms (2)

Low dose nortriptyline (10 mg/day)

High dose nortriptyline (>10-150 mg/day)

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Related Publications (3)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Intervention Hierarchy (Ancestors)

Data Sharing

Source record

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

Primary Completion

First Submitted

First Posted

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (7)

Study Arms (2)

Low dose nortriptyline (10 mg/day)

High dose nortriptyline (>10-150 mg/day)

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Related Publications (3)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Intervention Hierarchy (Ancestors)

Data Sharing

Source record