Thalassemia MajorPAH2010NCT01496963
Prevalence of Pulmonary Hypertension (PAH) in Patients With Thalassemia
An observational study of Thalassemia Major and Thalassemia Intermedia, run by Ente Ospedaliero Ospedali Galliera at 8 sites in Italy.
Trial summary
This is a multicenter observational case-control analysis lasting 12 months aimed at determining the prevalence of pulmonary hypertension (PAH) in patients with Thalassemia Major and Intermedia. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Thalassemia Major, Thalassemia Intermedia, Pulmonary Arterial Hypertension
- What is being tested?
- Physician standard-of-care according to ESC/ERS Guidelines
- How many people
- 1,500 participants
- Where
- 8 sitesItaly
- Study dates
- Jan 2012to Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with Thalassemia Major and Intermedia studied by echocardiography in the six months prior to the beginning of the study
Who may be able to join
- Patients with Thalassemia Major Patients or Intermediate referring to Centres using Web-Thal medical record (a clinical data sheet used for congenital anemias. Info: www.thalassemia.it)
Who cannot join
- Patients who are considered potentially unreliable and/or not cooperative
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Italy8 sites
Divisione di Ematologia Ospedale Perrino
Brindisi, 72100
Clinica pediatrica Ospedale Microcitemico
Cagliari, 09123
DH Microcitemia dell'adulto Ospedale Microcitemico
Cagliari, 09123
Centro della Microcitemia e delle Anemie Congenite -Ematologia e Cardiologia E.O. Ospedali Galliera
Genoa, 16128
Centro Anemie Congenite Università di Milano IRCCS Ospedale Maggiore Policlinico
Milan, 20162
Dipartimento di pediatria "F.Fede" A.O. Universitaria FedericoII di Napoli
Naples, 80131
U.O.C- Cardiologia Ospedale San Francesco
Nuoro, 8100
SCDU Microcitemie-Pediatria A.O. Universitaria S.Luigi Gonzaga di Orbassano
Orbassano, Turin, 10043
About this study
Official title: Observational Multicenter Study Lasting 12 Months to Determine the Prevalence of Pulmonary Hypertension (PAH) in Patients With Thalassemia Major and Intermedia and Verify the Suitability of Common Diagnostic Criteria in This Population
This is a multicenter observational case-control analysis lasting 12 months aimed at determining the prevalence of pulmonary hypertension (PAH) in patients with Thalassemia Major and Intermedia. The patients will be followed, treated and examined according to the best standard clinical practice dictated by the Italian Society for the study of Hemoglobinopathies (SITE), Thalassemia International Federation (TIF)and the Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC); European Respiratory Society (ERS); International Society of Heart and Lung Transplantation (ISHLT) guidelines.
Read the detailed description
The most recent International Classification of pulmonary arterial hypertension (PHA) include Hemoglobinopathies in Class I. At present there is no determination of the prevalence of this disease in a large population of thalassemic patients followed in a uniform way. The diagnostic criteria used for the normal population may not be suitable for a population such as thalassemia patients who present features like chronic anemia, iron overload, liver disease, endocrine disorders, etc.
The criteria used to define the disease (PHA) will be those ones dictated by the above mentioned guidelines.
Primary Objective of the study is the determination of the prevalence and severity of PHA in thalassemia syndromes, recently introduced in Class I of the Classification of PHA.
Secondary objectives are:
Critical evaluation of current diagnostic criteria derived from those applied to the general population, taking into account the peculiarities of the observed disease in the thalassemic population.
Evaluation of sensitivity and specificity of echocardiogram versus right cardiac catheterization (RHC).
Evaluation of the correlation between:
echocardiography and RHC; resistance and heart rate determined both by RHC and echocardiography; Determination of the patients resulted vasoreactive during RHC. Validation of sensitivity and specificity (sens/spec) of 6 minutes walking test (6MWT) and brain natriuretic peptide (BNP) in Thalassemia Major (TM) and Intermediate (TI) with reference to specific pulmonary hypertensive disease
In order to achieve the objectives of the study observed patients will be divided into group according to the following the criteria:
group a)
- Pulmonary artery pressure (PAP) assessed (by echocardiogram) < 36 mmHg or a tricuspid regurgitant jet velocity (TG) < 3 m/sec and data on PAP and mean left ventricular ejection fraction (LVEF) > 50% group b)
- PAP estimated (by echocardiography)> 40 mmHg or TG > 3.2 m / sec and LVEF> 50%
- As indicated by the Guidelines, patients b) with increased PAP (TG > 3.2 m / sec or > 40 mm Hg) will be further studied using RHC and vasoreactivity testing. Angio CAT, 6MWT and BNP. group c) - PAP estimated (by echocardiography) in the range of values > 3 m/sec (TG) and < 3.2 m / sec or > 36 mm Hg and <40 mmHg and LVEF > 50% Each case included both in group b) and c) will be paired with two controls included in the group a) to make the groups more comparable.
The group a) will serve as control group to compare the diagnostic methods evaluated as per protocol.
In order to divide the patients into the three groups specified above first it will be evaluated: PAP, LVEF% and TG assessed by echocardiographic examination performed in the six months prior to the beginning of the study (thalassemic patients have to perform echocardiography once a year to monitor cardiac function according to the guidelines)
Patients belonging to groups a), b) and c) will perform the following assessments:
- Clinical cardiac evaluation according to the New York Heart Association (NYHA) (functional class I to IV)
As per the International Guidelines, patients belonging to groups b) and c) have clinical indications to undergo Two-dimensional echocardiography-Doppler Duplex Scanner (PW) and color flow (CW) to determine the following parameters:
- End-systolic volume and left ventricular end diastolic, indexed according to body surface
- Percentage change of right ventricular areas (area diastolic/systolic area expressed as a percentage%)
- Tricuspid lateral annulus excursion Longitudinal (TAPS)
- Eccentricity Index (EI)
- TG
- Pulmonary resistance.
Moreover, patients belonging to group b), according to the International Guidelines have clinical indication to undergo RHC, diagnostic evaluation to rule out the presence of associated diseases and to measure:
- Pulmonary pressures
- Mean atrial pressure
- Pulmonary resistance
- Cardiac rate
- Vasoreactivity test
To compare the data derived from the RHC and the echocardiography the following echocardiographic parameters will be further evaluated:
Right atrial pressure; Cardiac output; Pulmonary wedge pressure
- Being tested
- Physician standard-of-care according to ESC/ERS Guidelines
- Keywords
- Thalassemia, Pulmonary Arterial Hypertension
- Medical subject headings
- beta-Thalassemia, Pulmonary Arterial Hypertension, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physician standard-of-care according to ESC/ERS GuidelinesOther
Physician standard-of-care
| Study group | Role | What they receive |
|---|---|---|
| group a) | Patients with pulmonary artery pressure (PAP) assessed (by echocardiogram) <36 mmHg or a tricuspid regurgitant jet velocity (TG) <3 m / sec and data on PAP and mean left ventricular ejection fraction (LVEF) > 50% Receives: Other: Physician standard-of-care according to ESC/ERS Guidelines | |
| group b) | Patients with:
PAP estimated (by echocardiography)> 40 mmHg or TG> 3.2 m / sec and LVEF> 50% As indicated by the Guidelines, patients b) with increased PAP (TG> 3.2 m / sec or> 40 mm Hg) will be further studied using RHC and vasoreactivity testing. Angio CAT, 6MWT and BNP. Receives: Other: Physician standard-of-care according to ESC/ERS Guidelines | |
| group c) | patients with PAP estimated (by echocardiography) in the range of values > 3 m / sec (TG) and <3.2 m / sec or> 36 mm Hg and <40 mmHg and LVEF> 50% Receives: Other: Physician standard-of-care according to ESC/ERS Guidelines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the prevalence
Determination of the prevalence, defined as the total number of cases in the population, divided by the number of individuals in the population.
Measured: 12 months
Secondary outcomes (1)
Critical evaluation of current diagnostic criteria
Critical evaluation of current diagnostic criteria taking into account the peculiarities of the observed of PHA in thalassemic patients.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2021
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Thalassemia MajorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ente Ospedaliero Ospedali Galliera
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01496963
- Sponsor's protocol ID
- PAH2010
- Acronym
- PAH2010
- Status last verified
- Aug 2022
- First submitted
- 14 Dec 2011
- Last updated
- 4 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC); European Respiratory Society (ERS); International Society of Heart and Lung Transplantation (ISHLT); Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009 Dec;34(6):1219-63. doi: 10.1183/09031936.00139009. Epub 2009 Sep 12. No abstract available.
PubMed 19749199Derchi G, Galanello R, Bina P, Cappellini MD, Piga A, Lai ME, Quarta A, Casu G, Perrotta S, Pinto V, Musallam KM, Forni GL; Webthal Pulmonary Arterial Hypertension Group*. Prevalence and risk factors for pulmonary arterial hypertension in a large group of beta-thalassemia patients using right heart catheterization: a Webthal study. Circulation. 2014 Jan 21;129(3):338-45. doi: 10.1161/CIRCULATIONAHA.113.002124. Epub 2013 Sep 30.
PubMed 24081970
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Multicenter Study Lasting 12 Months to Determine the Prevalence of Pulmonary Hypertension (PAH) in Patients With Thalassemia Major and Intermedia and Verify the Suitability of Common Diagnostic Criteria in This Population
- ClinicalTrials.gov ID
- NCT01496963
- Acronym / sponsor ID
- PAH2010 / PAH2010
- Keywords
- Thalassemia, Pulmonary Arterial Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Ente Ospedaliero Ospedali GallieraUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Dec 2021 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 22 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter observational case-control analysis lasting 12 months aimed at determining the prevalence of pulmonary hypertension (PAH) in patients with Thalassemia Major and Intermedia. The patients will be followed, treated and examined according to the best standard clinical practice dictated by the Italian Society for the study of Hemoglobinopathies (SITE), Thalassemia International Federation (TIF)and the Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC); European Respiratory Society (ERS); International Society of Heart and Lung Transplantation (ISHLT) guidelines.
Detailed description
The most recent International Classification of pulmonary arterial hypertension (PHA) include Hemoglobinopathies in Class I. At present there is no determination of the prevalence of this disease in a large population of thalassemic patients followed in a uniform way. The diagnostic criteria used for the normal population may not be suitable for a population such as thalassemia patients who present features like chronic anemia, iron overload, liver disease, endocrine disorders, etc.
The criteria used to define the disease (PHA) will be those ones dictated by the above mentioned guidelines.
Primary Objective of the study is the determination of the prevalence and severity of PHA in thalassemia syndromes, recently introduced in Class I of the Classification of PHA.
Secondary objectives are:
Critical evaluation of current diagnostic criteria derived from those applied to the general population, taking into account the peculiarities of the observed disease in the thalassemic population.
Evaluation of sensitivity and specificity of echocardiogram versus right cardiac catheterization (RHC).
Evaluation of the correlation between:
echocardiography and RHC; resistance and heart rate determined both by RHC and echocardiography; Determination of the patients resulted vasoreactive during RHC. Validation of sensitivity and specificity (sens/spec) of 6 minutes walking test (6MWT) and brain natriuretic peptide (BNP) in Thalassemia Major (TM) and Intermediate (TI) with reference to specific pulmonary hypertensive disease
In order to achieve the objectives of the study observed patients will be divided into group according to the following the criteria:
group a)
- Pulmonary artery pressure (PAP) assessed (by echocardiogram) < 36 mmHg or a tricuspid regurgitant jet velocity (TG) < 3 m/sec and data on PAP and mean left ventricular ejection fraction (LVEF) > 50% group b)
- PAP estimated (by echocardiography)> 40 mmHg or TG > 3.2 m / sec and LVEF> 50%
- As indicated by the Guidelines, patients b) with increased PAP (TG > 3.2 m / sec or > 40 mm Hg) will be further studied using RHC and vasoreactivity testing. Angio CAT, 6MWT and BNP. group c) - PAP estimated (by echocardiography) in the range of values > 3 m/sec (TG) and < 3.2 m / sec or > 36 mm Hg and <40 mmHg and LVEF > 50% Each case included both in group b) and c) will be paired with two controls included in the group a) to make the groups more comparable.
The group a) will serve as control group to compare the diagnostic methods evaluated as per protocol.
In order to divide the patients into the three groups specified above first it will be evaluated: PAP, LVEF% and TG assessed by echocardiographic examination performed in the six months prior to the beginning of the study (thalassemic patients have to perform echocardiography once a year to monitor cardiac function according to the guidelines)
Patients belonging to groups a), b) and c) will perform the following assessments:
- Clinical cardiac evaluation according to the New York Heart Association (NYHA) (functional class I to IV)
As per the International Guidelines, patients belonging to groups b) and c) have clinical indications to undergo Two-dimensional echocardiography-Doppler Duplex Scanner (PW) and color flow (CW) to determine the following parameters:
- End-systolic volume and left ventricular end diastolic, indexed according to body surface
- Percentage change of right ventricular areas (area diastolic/systolic area expressed as a percentage%)
- Tricuspid lateral annulus excursion Longitudinal (TAPS)
- Eccentricity Index (EI)
- TG
- Pulmonary resistance.
Moreover, patients belonging to group b), according to the International Guidelines have clinical indication to undergo RHC, diagnostic evaluation to rule out the presence of associated diseases and to measure:
- Pulmonary pressures
- Mean atrial pressure
- Pulmonary resistance
- Cardiac rate
- Vasoreactivity test
To compare the data derived from the RHC and the echocardiography the following echocardiographic parameters will be further evaluated:
Right atrial pressure; Cardiac output; Pulmonary wedge pressure
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| group a) | – | Other: Physician standard-of-care according to ESC/ERS GuidelinesPatients with pulmonary artery pressure (PAP) assessed (by echocardiogram) <36 mmHg or a tricuspid regurgitant jet velocity (TG) <3 m / sec and data on PAP and mean left ventricular ejection fraction (LVEF) > 50% |
| group b) | – | Other: Physician standard-of-care according to ESC/ERS GuidelinesPatients with: PAP estimated (by echocardiography)> 40 mmHg or TG> 3.2 m / sec and LVEF> 50% As indicated by the Guidelines, patients b) with increased PAP (TG> 3.2 m / sec or> 40 mm Hg) will be further studied using RHC and vasoreactivity testing. Angio CAT, 6MWT and BNP. |
| group c) | – | Other: Physician standard-of-care according to ESC/ERS Guidelinespatients with PAP estimated (by echocardiography) in the range of values > 3 m / sec (TG) and <3.2 m / sec or> 36 mm Hg and <40 mmHg and LVEF> 50% |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Thalassemia Major and Intermedia studied by echocardiography in the six months prior to the beginning of the study
Key inclusion criteria (1 listed)
- Patients with Thalassemia Major Patients or Intermediate referring to Centres using Web-Thal medical record (a clinical data sheet used for congenital anemias. Info: www.thalassemia.it)
Key exclusion criteria (1 listed)
- Patients who are considered potentially unreliable and/or not cooperative
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physician standard-of-care according to ESC/ERS GuidelinesPhysician standard-of-care | Other | group a), group b), group c) |
Primary outcome
Determination of the prevalence
Time frame: 12 months
Determination of the prevalence, defined as the total number of cases in the population, divided by the number of individuals in the population.
1 secondary outcome
Critical evaluation of current diagnostic criteria
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2022.
- Background: PubMed 19749199Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC); European Respiratory Society (ERS); International Society of Heart and Lung Transplantation (ISHLT); Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009 Dec;34(6):1219-63. doi: 10.1183/09031936.00139009. Epub 2009 Sep 12. No abstract available.
- Derived from this study: PubMed 24081970Derchi G, Galanello R, Bina P, Cappellini MD, Piga A, Lai ME, Quarta A, Casu G, Perrotta S, Pinto V, Musallam KM, Forni GL; Webthal Pulmonary Arterial Hypertension Group*. Prevalence and risk factors for pulmonary arterial hypertension in a large group of beta-thalassemia patients using right heart catheterization: a Webthal study. Circulation. 2014 Jan 21;129(3):338-45. doi: 10.1161/CIRCULATIONAHA.113.002124. Epub 2013 Sep 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thalassemia Major and Thalassemia Intermedia, run by Ente Ospedaliero Ospedali Galliera at 8 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of the prevalence (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01496963, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2022.