Clinical trial NCT04354350: Replication of the ONTARGET Antihypertensive Trial in Healthcare Claims Data
Official title: Replication of the ONTARGET Antihypertensive Trial in Healthcare Claims Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypertension
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 63744
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study will involve a new user, parallel group, cohort study design comparing telmisartan to ramipril. The patients will be required to have continuous enrollment during baseline period of 180 days before initiation of telmisartan or the comparator drug (cohort entry date). Follow-up for the outcome, begins the day after drug initiation. As in the trial, patients are allowed to take other antihypertensive medications during the study.

Brief summary: Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed description: This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Eligibility criteria: Please see: https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Eligible cohort entry dates: Market availability of telmistartan in the U.S. started on November 10, 1998, however, the Marketscan and Optum data are available at BWH only from Jan 1, 2003 and Jan 1, 2004, respectively. For Marketscan: Jan 1, 2003 -Dec 2017 (end of data availability). For Optum: Jan 1, 2004-June 30, 2019 (end of data availability).

Inclusion Criteria:

* Individuals 55 years of age with 1 of the following:

  * 1. Coronary artery disease

    * 1a. Previous myocardial infraction ( \> 2 days post uncomplicated MI)
    * 1b. Stable angina or unstable angina \> 30 days before informed consent and with documented evidence of multivessel coronary artery disease
    * 1c. Multi-vessel PTCA \>30 days before informed consent
    * 1d. Multi-vessel CABG surgery \> 4 years before informed consent, or with recurrent angina following surgery
  * 2. Peripheral artery disease

    * 2a. Previous limb bypass surgery or Previous limb bypass surgery or angioplasty
    * 2b. Previous limb or foot amputation
    * 2c. Intermittent claudication, with ankle:arm BP ratio =\< 0.80 on at least 1 side
    * 2d. Significant peripheral artery stenosis ( \> 50%) documented by angiography or non-invasive testing
  * 3. Cerebrovascular disease

    * 3a. Previous stroke
    * 3b. Transient ischemic attacks \>7 days and \<1 year before informed consent
  * 4. Diabetus mellitus

    * 4a. Diabetes mellitus High-risk diabetics with evidence of endorgan damage

Exclusion Criteria:

* 1. Medication use

  * 1a. Inability to discontinue ACE inhibitors or ARB
  * 1b. Known hypersensitivity or intolerance to ACE inhibitors or ARB (patient intolerant of ACE inhibitor can be enrolled in TRANSCEND)
* 2. Cardiovascular disease (HF)

  * 2a. Symptomatic congestive heart failure
  * 2b. Hemodynamically significant primary valvular or outflow tract obstruction
  * 2c. Constrictive pericarditis
  * 2d. Complex congenital heart disease
  * 2e. Syncopal episodes of unknown etiology \<3 months before informed consent
  * 2f. Planned cardiac surgery or PTCA \<3 months of informed consent
  * 2g. Uncontrolled hypertension on treatment (eg, BP \>160/100 mm Hg)
  * 2f. Heart transplant recipient
  * 2g. Stroke due to subarachnoid hemorrhage
* 3. Other conditions

  * 3a. Significant renal artery disease
  * 3b. Hepatic dysfunction
  * 3c. Uncorrected volume or sodium depletion
  * 3d. Primary hyperaldosteronism
  * 3e. Hereditary fructose intolerance
  * 3f. Other major noncardiac illness expected to reduce life expectancy or interfere with study participation
  * 3g. Simultaneously taking another experimental drug
  * 3h. Significant disability precluding regular follow-up visits
  * 3I. Unable or unwilling to provide written informed consent

Primary outcomes:
measure: Relative hazard of composite outcome of Heart Failure, Stroke, MI, and Mortality
timeFrame: [Time Frame: Through study completion (a median of ***118-123**** days)]
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham And Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shirley Wang, PhD, ScM
role: PRINCIPAL_INVESTIGATOR
References: