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    Summary
    EudraCT Number:2020-000236-22
    Sponsor's Protocol Code Number:Study_protocol_CODEX-P_ver2_1
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-19
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedDenmark - DHMA
    A.2EudraCT number2020-000236-22
    A.3Full title of the trial
    COPD EXacerbation and Pulmonary hypertension Trial
    - The effect of Sildenafil treatment to patients with COPD exacerbation and pulmonary hypertension
    Klinisk forsøg vedrørende behandling med Sildenafil til patienter med KOL og pulmonal hypertension
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial regarding the effect of Sildenafil treatment to patients with COPD and increased pressure in the respiratory system
    A.3.2Name or abbreviated title of the trial where available
    CODEX-P
    A.4.1Sponsor's protocol code numberStudy_protocol_CODEX-P_ver2_1
    A.5.4Other Identifiers
    Name:Research Ethics ComitteeNumber: H-18020463
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorChronic Obstructive Pulmonary Disease Trial Network (COP:TRIN)
    B.1.3.4CountryDenmark
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCOP:TRIN
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCOP:TRIN
    B.5.2Functional name of contact pointwww.coptrin.dk
    B.5.3 Address:
    B.5.3.1Street AddressKildegårdsvej 28
    B.5.3.2Town/ cityHellerup
    B.5.3.3Post code2900
    B.5.3.4CountryDenmark
    B.5.4Telephone number4528938168
    B.5.6E-mailjens.ulrik.jensen@regionh.dk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Vizarsin
    D.2.1.1.2Name of the Marketing Authorisation holderKrka, d.d., Novo mesto
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVizarsin
    D.3.2Product code Sildenafil
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSILDENAFIL
    D.3.9.1CAS number 139755-83-2
    D.3.9.4EV Substance CodeSUB10517MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number60 to 225
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    This study will investigate treatment of patients with chronic obstructive pulmonary disease (COPD), who experience frequent exacerbations (AECOPD). Only patients with a minimum of 2 moderate AECOPD or 1 severe AECOPD within 12 months will be able to participate. Furthermore they must pulmonary hypertension documented by echocardiography.
    E.1.1.1Medical condition in easily understood language
    Patients with Chronic Obstructive Lung Disease who has experienced more than 1 acute worsening of their condition within the last year and a documented increase of the pressure in the lungs.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10019203
    E.1.2Term Head spinning
    E.1.2System Organ Class 100000004854
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10033405
    E.1.2Term Pain head
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10019218
    E.1.2Term Headache NOS
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10000460
    E.1.2Term Acid dyspepsia
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 22.1
    E.1.2Level LLT
    E.1.2Classification code 10013947
    E.1.2Term Dyspepsia aggravated
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10013948
    E.1.2Term Dyspepsia and other specified disorders of function of stomach
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10019328
    E.1.2Term Heartburn-like dyspepsia
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10064536
    E.1.2Term Functional dyspepsia
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level LLT
    E.1.2Classification code 10012727
    E.1.2Term Diarrhea
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10023222
    E.1.2Term Joint pain
    E.1.2System Organ Class 100000004859
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10025012
    E.1.2Term Lumbo-sacral pain
    E.1.2System Organ Class 100000004859
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10028322
    E.1.2Term Muscle pain
    E.1.2System Organ Class 100000004859
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10033394
    E.1.2Term Pain epigastric
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10016046
    E.1.2Term Facial flushing
    E.1.2System Organ Class 100000004866
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10013614
    E.1.2Term Double vision
    E.1.2System Organ Class 100000004853
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10005604
    E.1.2Term Blood in urine
    E.1.2System Organ Class 100000004848
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10018801
    E.1.2Term Gynecomastia
    E.1.2System Organ Class 100000004872
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10060603
    E.1.2Term Hematospermia
    E.1.2System Organ Class 100000004872
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10002272
    E.1.2Term Anemia
    E.1.2System Organ Class 100000004851
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 22.1
    E.1.2Level LLT
    E.1.2Classification code 10034961
    E.1.2Term Photophobia aggravated
    E.1.2System Organ Class 100000004853
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10023139
    E.1.2Term Jaundice NOS
    E.1.2System Organ Class 100000004871
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10030042
    E.1.2Term Ocular hyperemia
    E.1.2System Organ Class 100000004853
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10051304
    E.1.2Term Retinal bleeding
    E.1.2System Organ Class 100000004853
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10005889
    E.1.2Term Blurry vision
    E.1.2System Organ Class 100000004853
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10046272
    E.1.2Term Upper abdominal pain
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10038263
    E.1.2Term Reflux oesophagitis
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10047706
    E.1.2Term Vomiting NOS
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10016558
    E.1.2Term Fever
    E.1.2System Organ Class 100000004867
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10024969
    E.1.2Term Lower respiratory tract infection NOS
    E.1.2System Organ Class 100000004862
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10048317
    E.1.2Term Myalgia aggravated
    E.1.2System Organ Class 100000004859
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10003990
    E.1.2Term Back pain (without radiation)
    E.1.2System Organ Class 100000004859
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10020922
    E.1.2Term Hypesthesia
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10027605
    E.1.2Term Migraine NOS
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10044572
    E.1.2Term Tremor limb
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10044570
    E.1.2Term Tremor finger
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10002856
    E.1.2Term Anxiety attack
    E.1.2System Organ Class 100000004873
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10022442
    E.1.2Term Insomnia NOS
    E.1.2System Organ Class 100000004873
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10011232
    E.1.2Term Coughing
    E.1.2System Organ Class 100000004855
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10040756
    E.1.2Term Sinusitis NOS
    E.1.2System Organ Class 100000004862
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10014210
    E.1.2Term Edema
    E.1.2System Organ Class 100000004867
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10014211
    E.1.2Term Edema (NOS)
    E.1.2System Organ Class 100000004867
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The aim of this study is to clarify
    1) whether the prognosis (days alive and out of hospital in 12 months) among patients with AECOPD and pulmonary hypertension can be improved by treatment with the phosphodiesterase inhibitor, sildenafil.
    E.2.2Secondary objectives of the trial
    2) the prevalence of pulmonary hypertension in patients admitted for AECOPD.

    3) if the prognosis in AECOPD combined with pulmonary hypertension worsens the clinical status and prognosis
    of AECOPD.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    CODEX-P: COPD exacerbation and pulmonary hypertension trial - a cohort study.

    The study is also described in the study protocol (date 18/08-2020).

    The objective is to determine the prevalence of pulmonary hypertension among patients admitted with AECOPD.
    E.3Principal inclusion criteria
    - COPD (verified by respiratory specialist based on clinical assessment and
    spirometry)
    - Acute hospitalization with an action diagnosis of “AECOPD”
    - Tricuspid return (TR) gradient ≥ 40 mmHg assessed by echocardiography done by a cardiolog
    specialist or a main physician with special interestand adequate training in
    echocardiography
    - “Stabile phase” TR gradient <40 mmHg (at day 25-35 after admission)
    - Informed consent
    E.4Principal exclusion criteria
    - Diagnosed with any type of pulmonary hypertension
    - Diagnosed with left or right sided heart failure
    - Male <40 years
    - Women <55 years
    - Non-menopausal woman >55 years*
    - Severe mental illness or linguistic problems that considerably complicate
    cooperation
    - Known allergy to Vizarsin (Sildenafil)
    - Takes Vizarsin (Sildenafil) with other indication with consumption ≥50 mg/week

    *defined as have had ≥ 1 menstruation within the last 12 months
    E.5 End points
    E.5.1Primary end point(s)
    Time alive and discharged from hospital within 365 days from baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    365 days
    E.5.2Secondary end point(s)
    - Time to prednisolone and/or antibiotic-requiring AECOPD or death in primary or
    secondary care within 365 days
    - Death within 90 days
    - Death within 12 months
    - Number of readmissions with COPD exacerbations within 12 months
    - A live and without AECOPD on day 365
    - Number of days with non-invasive ventilation (NIV) or mechanical ventilation
    treatment during 365 days
    - Change in PaO2 from baseline to day 4
    - Change in PaCO2 from baseline to day 4
    - pH on day 4
    - Change in FEV1 from baseline to day 90 months
    - Change in COPD Assessment Test (CAT) from baseline to day 29
    - Change in body mass index (BMI) from baseline to day 90
    - Delta TR gradient from baseline to day 90
    E.5.2.1Timepoint(s) of evaluation of this end point
    365 days
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Standard treatment
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The trial ends after the last follow up, which will be 12 months after the last patient is included
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 98
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state116
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Not different from the expected standard treatment
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Chronic Obstructive Pulmonary Disease Trial Network (COP:TRIN)
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-12-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-08-15
    P. End of Trial
    P.End of Trial StatusOngoing
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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