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AMR Drug RepurposingSmart Screeningresearch prototype

Metolazone

FDA-approved product (tablet, oral), marketed as Diulo, Metolazone, Mykrox and 1 more.

Registered studies
36
Lab records
0
Pathogens at ≥40%
2 of 4

Chemical structure

Chemical structure of Metolazone
A drawing shows what the molecule is, not what it does.

Existing / approved use

Documented · FDA, WHO, ChEMBL

Approved for

  • Cardiovascular disease
  • Congestive heart failure
  • Heart failure
  • Hypertension
  • Preeclampsia

Indications ChEMBL records as approved, from FDA and DailyMed labels. Label ↗

WHO therapeutic group
Sulfonamides, plain
FDA pharmacologic class
Thiazide-like Diuretic FDA label ↗
Anti-infective classification
Not classified as an anti-infective.

Repurposing investigation

This medicine is being investigated here for AI-predicted antimicrobial activity against M. tuberculosis and MRSA. It was surfaced computationally for further investigation; it is not an established treatment for these infections.

AI-predicted activity

AI prediction · nothing measured
  • MRSA42.2% AI-predicted activityAt or above the ≥40% mark this site uses to surface candidates.
  • E. coli31.3% AI-predicted activityBelow the ≥40% mark this site uses to surface candidates.
  • K. pneumoniae26.6% AI-predicted activityBelow the ≥40% mark this site uses to surface candidates.
  • M. tuberculosis59.0% AI-predicted activityAt or above the ≥40% mark this site uses to surface candidates.

A model’s estimate of laboratory activity against each pathogen species. It is not clinical effectiveness.

Evidence

Clinical and experimental

Documented evidence

Clinical

36registered studies name this medicine, for any condition. See them below.

Experimental

No evidence found

No laboratory measurement against the four pathogens in the ChEMBL records loaded here.

Open Metolazone in ChEMBL Registered studies below

Docking

Computational · nothing measured

Dihydrofolate reductase ↗ (E. coli)

-8.0 kcal/mol

0better fit →-12

KPC-2 carbapenemase ↗ (K. pneumoniae)

-8.0 kcal/mol

0better fit →-12

Enoyl-ACP reductase (InhA) ↗ (M. tuberculosis)

-7.7 kcal/mol

0better fit →-12

Dihydrofolate reductase ↗ (MRSA)

-7.4 kcal/mol

0better fit →-12

AutoDock Vina, one experimentally solved protein per pathogen. This project’s screening target is -7.0 kcal/mol, its own mark rather than a universal cutoff. A docking score is a structural hypothesis, not proof of binding, and requires experimental validation.

Other medicines to investigate

AI prediction · nothing measured

Other repurposing candidates: approved medicines besides Metolazone with AI-predicted activity ≥40% against the chosen pathogen, leaving out existing antimicrobials. They are computational candidates for further investigation, not alternatives and not recommendations.

Sorted by AI-predicted activity, high to low. The order is not a ranking of which medicine is better.

Registered studies

A registration describes a study; it does not establish a positive result.

  • ACEI or ARB and COVID-19 Severity and Mortality in US Veterans

    NCT04467931 · start 2020-01-19

    Registered record
    Registry ID
    NCT04467931
    Conditions
    Hypertension; COVID
    Interventions
    ACEI/ARB; Non-ACEI/ARB; ACEI; ARB
    Study type
    OBSERVATIONAL
    Phase
    Not recorded
    Registry status
    Completed
    Start
    2020-01-19
    Completion
    2020-12-31
    Enrolment
    22,213

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionHypertension; COVID
    InterventionACEI/ARB; Non-ACEI/ARB; ACEI; ARB
    PhaseNot recorded
    Registry statusCompleted

  • Safety and Efficacy of Early, seQUential Oral dIuretic Nephron blockAde In Acute Heart Failure

    NCT04062760 · start 2019-12-01

    Registered record
    Registry ID
    NCT04062760
    Conditions
    Acute Heart Failure
    Interventions
    Standard diuretic therapy; Early sequential nephron blockade
    Study type
    INTERVENTIONAL
    Phase
    Phase 4
    Registry status
    Unknown
    Start
    2019-12-01
    Completion
    2024-12-01
    Enrolment
    206

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionAcute Heart Failure
    InterventionStandard diuretic therapy; Early sequential nephron blockade
    PhasePhase 4
    Registry statusUnknown

  • Sequential Nephron Blockade in Acute Heart Failure

    NCT04163588 · start 2019-10-01

    Registered record
    Registry ID
    NCT04163588
    Conditions
    Acute Heart Failure
    Interventions
    Metolazone; Loop Diuretics
    Study type
    INTERVENTIONAL
    Phase
    Phase 3
    Registry status
    Unknown
    Start
    2019-10-01
    Completion
    2020-12-31
    Enrolment
    310

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionAcute Heart Failure
    InterventionMetolazone; Loop Diuretics
    PhasePhase 3
    Registry statusUnknown

  • Exploring Diuretics Effective Management in Acute Decompensated Heart Failure, EDEMA Trial

    NCT03863626 · start 2019-03-31

    Registered record
    Registry ID
    NCT03863626
    Conditions
    Acute Decompensated Heart Failure; Diuretics Resistance
    Interventions
    Frusemide IV shots; Frusemide IV infusion
    Study type
    INTERVENTIONAL
    Phase
    Not applicable
    Registry status
    Unknown
    Start
    2019-03-31
    Completion
    2021-12
    Enrolment
    400

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionAcute Decompensated Heart Failure; Diuretics Resistance
    InterventionFrusemide IV shots; Frusemide IV infusion
    PhaseNot applicable
    Registry statusUnknown

  • Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

    NCT03746002 · start 2019-01-01

    Registered record
    Registry ID
    NCT03746002
    Conditions
    Fluid Overload; Heart Failure Acute
    Interventions
    Metolazone 60 minutes prior to furosemide; Metolazone concurrently with furosemide
    Study type
    INTERVENTIONAL
    Phase
    Phase 4
    Registry status
    Terminated
    Start
    2019-01-01
    Completion
    2020-01-10
    Enrolment
    3

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionFluid Overload; Heart Failure Acute
    InterventionMetolazone 60 minutes prior to furosemide; Metolazone concurrently with furosemide
    PhasePhase 4
    Registry statusTerminated

  • Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance

    NCT03574857 · start 2018-06-01

    Registered record
    Registry ID
    NCT03574857
    Conditions
    Heart Failure; Heart Failure With Reduced Ejection Fraction; Heart Failure Acute; Cardiovascular Diseases
    Interventions
    Metolazone Oral Tablet; Chlorothiazide Injection
    Study type
    INTERVENTIONAL
    Phase
    Phase 4
    Registry status
    Terminated
    Start
    2018-06-01
    Completion
    2021-01-01
    Enrolment
    5

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionHeart Failure; Heart Failure With Reduced Ejection Fraction; Heart Failure Acute; Cardiovascular Diseases
    InterventionMetolazone Oral Tablet; Chlorothiazide Injection
    PhasePhase 4
    Registry statusTerminated

  • Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure

    NCT02606253 · start 2016-02

    Registered record
    Registry ID
    NCT02606253
    Conditions
    Heart Failure
    Interventions
    tolvaptan; Chlorothiazide; Metolazone
    Study type
    INTERVENTIONAL
    Phase
    Phase 4
    Registry status
    Completed
    Start
    2016-02
    Completion
    2018-10-31
    Enrolment
    60

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionHeart Failure
    Interventiontolvaptan; Chlorothiazide; Metolazone
    PhasePhase 4
    Registry statusCompleted

  • AiDing Diuresis wIth Tolvaptan (ADD-IT)

    NCT02646540 · start 2016-01

    Registered record
    Registry ID
    NCT02646540
    Conditions
    Cardiomyopathy; Congestive Heart Failure
    Interventions
    Tolvaptan 30 mg + IV Diuretics; Metolazone 5 mg + IV Diuretics; 2.5 times the Diuretics Dose
    Study type
    INTERVENTIONAL
    Phase
    Phase 1
    Registry status
    Completed
    Start
    2016-01
    Completion
    2018-12-30
    Enrolment
    14

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionCardiomyopathy; Congestive Heart Failure
    InterventionTolvaptan 30 mg + IV Diuretics; Metolazone 5 mg + IV Diuretics; 2.5 times the Diuretics Dose
    PhasePhase 1
    Registry statusCompleted

  • Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)--A Single Center Pilot Study.

    NCT02620384 · start 2015-10-01

    Registered record
    Registry ID
    NCT02620384
    Conditions
    Acute Decompensated Heart Failure
    Interventions
    Experimental: Placebo; Experimental: Metolazone
    Study type
    INTERVENTIONAL
    Phase
    Phase 3
    Registry status
    Terminated
    Start
    2015-10-01
    Completion
    2017-12-29
    Enrolment
    147

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionAcute Decompensated Heart Failure
    InterventionExperimental: Placebo; Experimental: Metolazone
    PhasePhase 3
    Registry statusTerminated

  • Aquaresis Utility for Hyponatremic Acute Heart Failure Study

    NCT02183792 · start 2014-12

    Registered record
    Registry ID
    NCT02183792
    Conditions
    Heart Failure
    Interventions
    Tolvaptan; Furosemide
    Study type
    INTERVENTIONAL
    Phase
    Phase 4
    Registry status
    Completed
    Start
    2014-12
    Completion
    2018-03
    Enrolment
    33

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionHeart Failure
    InterventionTolvaptan; Furosemide
    PhasePhase 4
    Registry statusCompleted

  • Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure

    NCT05633758 · start 2014-03

    Registered record
    Registry ID
    NCT05633758
    Conditions
    Acute Decompensated Heart Failure
    Interventions
    Placebo; Metolazone
    Study type
    INTERVENTIONAL
    Phase
    Phase 2
    Registry status
    Withdrawn
    Start
    2014-03
    Completion
    2016-03
    Enrolment
    0

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionAcute Decompensated Heart Failure
    InterventionPlacebo; Metolazone
    PhasePhase 2
    Registry statusWithdrawn

  • A Prospective, Single-center, Randomized, Controlled, Open-label, Pilot Study to Compare the Effectiveness and Safety of DIuretics Add-On Strategy in Acute Decompensated Heart Failure Patients (DIOS II)

    NCT02047422 · start 2014-01

    Registered record
    Registry ID
    NCT02047422
    Conditions
    Congestive Heart Failure
    Interventions
    Furosemide; metolazone; furosemid/spironolactone; metolazone/spironolactone
    Study type
    INTERVENTIONAL
    Phase
    Not applicable
    Registry status
    Withdrawn
    Start
    2014-01
    Completion
    2016-02
    Enrolment
    0

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionCongestive Heart Failure
    InterventionFurosemide; metolazone; furosemid/spironolactone; metolazone/spironolactone
    PhaseNot applicable
    Registry statusWithdrawn

  • Protocolized Diuretic Strategy in Cardiorenal Failure

    NCT01921829 · start 2013-11

    Registered record
    Registry ID
    NCT01921829
    Conditions
    Cardiac Failure; Renal Failure; Kidney Failure
    Interventions
    Protocolized Diuretic Strategy
    Study type
    INTERVENTIONAL
    Phase
    Phase 4
    Registry status
    Terminated
    Start
    2013-11
    Completion
    2015-11
    Enrolment
    19

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionCardiac Failure; Renal Failure; Kidney Failure
    InterventionProtocolized Diuretic Strategy
    PhasePhase 4
    Registry statusTerminated

  • A Prospective, Single-center, Open-label, Pilot Study to Compare the Effectiveness and Safety of Diuretics Add-On Strategy in Chronic Heart Failure Patients (DIOS 1)

    NCT01817803 · start 2013-03

    Registered record
    Registry ID
    NCT01817803
    Conditions
    Congestive Heart Failure
    Interventions
    furosemide/no spironolactone; metolazone/no spironolactone; furosemid/spironolactone; metolazone/spironolactone
    Study type
    INTERVENTIONAL
    Phase
    Not applicable
    Registry status
    Withdrawn
    Start
    2013-03
    Completion
    2015-12
    Enrolment
    0

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionCongestive Heart Failure
    Interventionfurosemide/no spironolactone; metolazone/no spironolactone; furosemid/spironolactone; metolazone/spironolactone
    PhaseNot applicable
    Registry statusWithdrawn

  • Stop Hypernatremia, Use Metolazone, for Aggressive, Controlled, Effective Diuresis

    NCT01617798 · start 2012-06

    Registered record
    Registry ID
    NCT01617798
    Conditions
    Respiratory Failure; Volume Overload; Hypernatremia
    Interventions
    Supplemental metolazone diuresis; Placebo Comparator: Control-- furosemide (lasix) only
    Study type
    INTERVENTIONAL
    Phase
    Not applicable
    Registry status
    Withdrawn
    Start
    2012-06
    Completion
    2013-06
    Enrolment
    0

    As stored from ClinicalTrials.gov. Registration describes a study; it does not mean the study worked.

    ConditionRespiratory Failure; Volume Overload; Hypernatremia
    InterventionSupplemental metolazone diuresis; Placebo Comparator: Control-- furosemide (lasix) only
    PhaseNot applicable
    Registry statusWithdrawn