Metabolism Informed Smoking Treatment: The MIST RCT

NCT04590404 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: VICC THO 20465R01CA232516-03
• Study Type: interventional
• Target: 606
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 3 randomized controlled trial will test Metabolism-Informed Smoking Treatment (MIST), a precision approach to smoking treatment that biologically tailors medication selection to nicotine metabolism.

Conditions

Smoking

Outcome Measures

Primary Outcomes (1)

• Biochemically-validated Past 7-day Point Prevalence Tobacco Abstinence

  6 months

Secondary Outcomes (3)

• Biochemically-validated Past 7-day Point Prevalence Tobacco Abstinence

  12 months

• Self-reported Medication Adherence Over the Past 7 Days

  1, 3 months

• Self-reported Receipt of Prescription for Smoking Cessation Medication Subsequent to the Initial Study Medication Prescription

  Up to 12 months after hospital discharge

Study Arms (2)

MIST (Metabolism-Informed Smoking Treatment)

EXPERIMENTAL

At hospital discharge, participants randomized to the MIST precision care arm will receive a prescription for medication (either varenicline or NRT). Post discharge, participants will receive automated phone calls via TelASK to promote continued engagement. Medication prescriptions will be informed by nicotine metabolism (i.e., NMR result) such that faster metabolizers are prescribed varenicline and slower metabolizers are prescribed NRT.

Behavioral: Post-discharge automated phone calls (IVR) with option to connect with a tobacco coach.; Drug: Nicotine Replacement Therapy; Drug: Varenicline; Other: Metabolism Informed Smoking Treatment (Nicotine metabolite ratio (NMR)-based selection of pharmacotherapy)

Usual Care

ACTIVE COMPARATOR

At hospital discharge, participants randomized to the Usual Care arm will receive a prescription for medication (either varenicline or NRT). Post discharge, participants will receive automated phone calls via TelASK to promote continued engagement. Medication prescription will not be informed by nicotine metabolism.

Behavioral: Post-discharge automated phone calls (IVR) with option to connect with a tobacco coach.; Drug: Nicotine Replacement Therapy; Drug: Varenicline

Interventions

Metabolism Informed Smoking Treatment (Nicotine metabolite ratio (NMR)-based selection of pharmacotherapy) OTHER

Nicotine metabolite ratio (NMR)-based selection of pharmacotherapy. NMR is a blood test to measure how fast the body breaks down nicotine.

MIST (Metabolism-Informed Smoking Treatment)

Post-discharge automated phone calls (IVR) with option to connect with a tobacco coach. BEHAVIORAL

Automated calls to assess smoking status, medication use, and additional support for quit attempt.

MIST (Metabolism-Informed Smoking Treatment); Usual Care

Nicotine Replacement Therapy DRUG

FDA-approved forms of nicotine replacement therapy for smoking cessation.

MIST (Metabolism-Informed Smoking Treatment); Usual Care

Varenicline DRUG

FDA-approved smoking cessation medication.

Also known as: Chantix

MIST (Metabolism-Informed Smoking Treatment); Usual Care

Eligibility Criteria

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

You may qualify if:

• be 18 years or older
• be enrolled in an insurance plan that supports prescription coverage for smoking cessation medication (such as Medicare part D, Medicaid, or private insurance) to facilitate bedside delivery of medications prior to hospital discharge
• have a regular provider/PCP
• agree to quit or try to quit smoking upon hospital discharge
• be a daily smoker when smoking normally during the month prior to entering the hospital
• be medically eligible to use varenicline
• be medically eligible to use nicotine replacement therapy
• have received discharge medication recommendations from a tobacco counselor
• agree to take smoking cessation medication (i.e., varenicline OR nicotine replacement therapy) home and consider using it
• have a cell phone or landline that can be reached directly (i.e., without transfer)
• have a permanent address where they live and can receive mail
• estimated life expectancy of at least one year or greater

You may not qualify if:

• insufficient time to perform and complete the enrollment process
• barrier to effective communication (including low English proficiency)
• not cognitively able to participate in the study
• too ill, on hospice, or physically unable to participate in the follow-up process
• previously completed the MIST study or is currently enrolled in a quit smoking study that involves a medication-based treatment
• estimated life expectancy of less than one year

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Vanderbilt University Medical Center ViTAL, Vanderbilt Center for Tobacco, Addiction, and Lifestyle General Internal Medicine and Public Health 2525 West End Ave, Suite 450

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Smoking

Interventions

Nicotine Replacement Therapy; Varenicline

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Limitations and Caveats

For context, this study began in 2020 at the start of the 2019 COVID pandemic, and was subject to delays associated with this global emergency. Additionally, in 2021 the study was impacted by the global recall of varenicline.

Results Point of Contact

• Title: Dr. Hilary Tindle
• Organization: Vanderbilt University Medical Center

hilary.tindle@vumc.org

(615) 875-9726

Study Officials

• Hilary Tindle, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 19, 2020
• Study Start: November 17, 2020
• Primary Completion: May 20, 2024
• Study Completion: November 22, 2024
• Last Updated: December 5, 2025
• Results First Posted: June 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)