Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis (MAVRIC)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 800
- 试验地点
- 15
- 主要终点
- Time to death, non-elective hospitalization, or lung transplantation
研究概览
简要总结
This is a randomized, placebo-controlled trial of metformin in 400 participants with idiopathic pulmonary fibrosis (IPF) who are at high risk of adverse clinical outcomes based on a proteomic classifier. The primary objective is to assess the safety and efficacy of metformin compared to placebo in participants with IPF who are at high-risk for adverse clinical events.
Approximately 800 participants with IPF will be screened. 400 participants who are at high risk for adverse clinical events (proteomic signature present) will be randomized into receiving metformin (n~200) or matching placebo (n~200). Participants that meet the eligibility criteria but do not have the proteomic signature (proteomic signature absent) will be contacted by phone at 12 and 24 months to review medical history.
详细描述
This is a multi-center, randomized, double-blind, placebo-controlled trial, of metformin or placebo in 400 participants with idiopathic pulmonary fibrosis (IPF) who are at high risk of adverse clinical outcomes based on a proteomic classifier.
Eligible participants will be placed into 2 groups depending on the results of their proteomic signature blood test done at the Screening Visit (Visit 0).
- Eligible participants who have the proteomic signature present will be randomized in a 1:1 fashion to either metformin at Visit 1 (Enrollment/Baseline) and attend follow-up visits at Months 1, 3, 6, 12, 18, 24, and a follow-up phone call at 25 months. Randomization will be stratified by background FDA-approved IPF therapy (yes/no) and DM status (yes/no).
- Eligible participants who are proteomic signature absent will be asked to complete 2 follow-up remote visits at Months 12 and 24.
The metformin starting dose will be 500 mg daily of extended-release formulation or matching placebo. The dose will be increased by 500 mg every 14 days to a total target daily dose of 1500 mg. Participants will be followed for a minimum of 12 months and a maximum of approximately 25 months, depending on the date of randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •IPF diagnosis by enrolling investigator (following the 2022 updated guidelines on diagnosis and management of IPF)
- •Age 40 years or older
- •HbA1c < 9% at screening
- •High risk by proteomic signature (proteomic signature present) for participants randomized only (for participants randomized only; participants that are proteomic signature absent will undergo remote study assessments at 12 and 24 months only).
- •If on FDA-approved treatment(s) for IPF, on a stable dose for at least 8 weeks prior to randomization
- •Ability to provide informed consent
排除标准
- •Taking metformin within 3 months of randomization
- •Allergy or intolerance to metformin
- •Use of insulin or insulin secretagogue(s) at randomization
- •Pregnancy, planning to become pregnant, or lactating
- •Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year during study participation
- •History of biochemically-confirmed acidosis (lactate > 5.0 mmol/L)
- •Estimated glomerular filtration rate less than 45 mL/min/1.73 m2 at screening
- •Moderate-to-severe liver disease, decompensated heart failure, or any other condition that may make the participant unsuitable for inclusion as assessed by the study investigator at each site
- •Receipt of an investigational study agent as part of a therapeutic trial within 30 days of the Screening Visit (Visit 0)
- •Continuous supplemental oxygen use at rest greater than 2 L/min
- •Unable to swallow pills
- •Taking a medication that has a major interaction with metformin, including acetazolamide (Diamox), cimetidine (Tagamet), dolutegravir, gatifloxacin, levoketoconazole, ranolazine, or carbonic anhydrase inhibitors. Occasional use of carbonic anhydrase inhibitors for travel is permitted.
- •Current alcohol intake ≥ 15 drinks per week in men, ≥ 8 drinks per week in women or ≥ 5 drinks per occasion in men, ≥ 4 drinks per occasion in women
- •Listed for transplant at the time of randomization
研究组 & 干预措施
Proteomic Signature Present - Placebo
200 participants who have a screening blood test result that is proteomic signature present will be randomized to matching placebo 12 to 24 months depending on time of enrollment into the trial.
干预措施: Matching Placebo (Drug)
Proteomic Signature Absent
Participants that meet the eligibility criteria but do have a screening blood test result that is proteomic signature absent (about 400 participants) will be asked to attend 2 follow-up remote visits at 12 and 24 months. This arm will be observational only.
Proteomic Signature Present - Metformin
200 participants who have a screening blood test result that is proteomic signature present will be randomized to oral metformin at a total target daily dose of 1500mg per day for 12 to 24 months depending on time of enrollment into the trial.
干预措施: Metformin (Drug)
结局指标
主要结局
Time to death, non-elective hospitalization, or lung transplantation
时间窗: Baseline (visit 1) to up to 24 months
Clinical composite measure defined as the time from randomization to the first occurrence of any of its three components: all-cause mortality, first unplanned (non-elective) hospitalization, or lung transplantation.
次要结局
- Change in Forced Vital Capacity (FVC)(Baseline (visit 1) to 12 months)
- Time to all-cause mortality(Baseline (visit 1) to up to 24 months)
- Time to first non-elective hospitalization(Baseline (visit 1) to up to 24 months)
- Time to lung transplantation(Baseline (visit 1) to up to 24 months)
- Time to respiratory hospitalization(Baseline (visit 1) to up to 24 months)
- Change in Forced Vital Capacity (FVC) % Predicted(Baseline (visit 1) to 12 months)
- Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) corrected for hemoglobin.(Baseline (visit 1) to 12 months.)
- Change in Six-Minute Walk Distance (6MWD)(Baseline (visit 1) to 12 months)
- Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Impacts Questionnaire(Baseline (visit 1) to 12 months)
- Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Impacts Questionnaire(Baseline (visit 1) to 24 months)
- Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Symptoms Questionnaire(Baseline (visit 1) to 12 months)
- Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Symptoms Questionnaire(Baseline (visit 1) to 24 months)
- Change in patient reported outcomes scores for the R-Scale-PF(Baseline (visit 1) to 12 months)
- Change in patient reported outcomes scores for the R-Scale-PF(Baseline (visit 1) to 24 months)
- Change in Fatigue Severity Scale Score(From baseline (visit 1) to 12 months)
- Change in Fatigue Severity Scale Score(Baseline (visit 1) to 24 months)
- Incidence of Major Adverse Cardiac Events (MACE)(Baseline (visit 1) through final follow-up visit)
- Rate of non-elective hospitalization(Baseline (visit 1) to 12 months)
- Rate of non-elective hospitalization from baseline to 24 months(Baseline (visit 1) to 24 months)
- Rate of Respiratory Hospitalizations(Baseline (visit 1) to 12 months)
- Rate of Respiratory Hospitalizations(Baseline (visit 1) to 24 months)
研究者
Fernando J Martinez
Professor
University of Massachusetts, Worcester