Cardiovascular DiseasesPhase 2NCT00115349

Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases

A Phase 2 study testing Deferoxamine and Deferiprone (L1) in people with Cardiovascular Diseases and Heart Diseases, run by Carelon Research at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Cardiovascular Diseases, Heart Diseases, Beta-Thalassemia
What is being tested?: Deferoxamine and Deferiprone (L1)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 6 sitesUnited States
Study dates: Jun 2005to Apr 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Transfusion-dependent beta-thalassemia (eight or more transfusion episodes in the previous year)
Left ventricular ejection fraction by MRI less than or equal to 56% by balanced steady-state free precession (SSFP) or 63% by spoiled gradient recalled echo (SPGR)
Currently on treatment with subcutaneous or intravenous DFO; participants must be willing and able to chelate 7 days per week 12 - 24 hours per day
Serum ferritin greater than 1000 µg/L or ferritin between 500 µg/L and 1000 µg/L and cardiac T2* less than 20 ms

Who cannot join

Pacemaker, severe claustrophobia, or other contraindications to MRI; severe congestive heart failure (New York Heart Association Classification IV); congenital or acquired valvular heart disease significant enough to require surgery or medications
Currently receiving treatment for hepatitis; renal insufficiency defined by a clinically significant abnormal serum creatinine with a calculated creatinine clearance of less than 50 ml/min according to the Cockroft formula
A neutrophil count less than 1.5 x 109/L on two or more occasions at least 4 weeks apart within the past year and not associated with an acute viral illness or a platelet count less than 80 x 109/L on two or more occasions at least 4 weeks apart within the past year
Treatment with L1 or Exjade during the previous 2 weeks or previous adverse experience to L1 requiring suspension
Infection with HIV
Active participation in other investigational drug or device studies

Show all 11Show fewer

Unwilling to consider treatment with DFO at a dose of 50-60 mg/kg 12-24 hours per day 7 days per week
Women who are pregnant or breast feeding
Systemic infection or cardiovascular, hepatic, renal, pulmonary, or gastrointestinal disease that would prevent patients from undergoing any of the study-required treatments or procedures or requires treatment with any contraindicated medication(s)
Presence of any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient's compliance with the protocol; may include but is not limited to alcohol or drug abuse
For women of child-bearing potential, an inability or unwillingness to use a highly effective method of contraception (e.g., implants, injectables, combined oral contraceptives, or some intrauterine devices)

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Children's Hospital
Boston, Massachusetts, 02115
Children's Memorial Hospital
Chicago, Illinois, 60614-3394
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Weill Medical College of Cornell University
New York, New York, 10021
Children's Hospital
Oakland, California, 94609
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4399

Other trials in United States

About this study

Official title: Thalassemia Clinical Research Network - Cardiac L1/DFO Trial

The purpose of this study is to determine whether left ventricular function improves more rapidly with deferoxamine (DFO) and deferiprone (L1) combination therapy than with DFO monotherapy in patients with thalassemia and decreased ejection fractions. Secondary aims include evaluating changes in myocardial iron burden using T2* and estimating the relative incidence and severity of chelator-induced toxicity.

Read the detailed description

DESIGN NARRATIVE:

Participants will be randomized to 1 year of treatment with L1/DFO combination therapy or DFO monotherapy. At baseline, 6 months, and 1 year on therapy, cardiac function will be assessed by MRI measurement of left ventricular ejection fraction (LVEF), T2*, Holter monitoring, and electrocardiography. Additional monitoring for safety includes weekly blood testing, monthly visits, and periodic eye and ear exams.

Conditions: Cardiovascular Diseases, Heart Diseases, Beta-Thalassemia
Being tested: Deferoxamine, Deferiprone (L1)
Medical subject headings: Cardiovascular Diseases, Heart Diseases, beta-Thalassemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DeferoxamineDrug
Also called DFO
Deferoxamine will be given daily for 12-24h/day 7 days a week either subcutaneous or intravenous at up to 50-60 mg/kg/day.
Deferiprone (L1)Drug
Also called L1
The dose of L1, 75mg/kg in three divided oral doses, is the maximum dose at which toxicity has been tested in prospective trials

Study groups in NCT00115349
Study group	Role	What they receive
L1/DFO	Experimental	Deferoxamine (DFO) and deferiprone (L1) combination therapy Receives: Drug: Deferoxamine; Drug: Deferiprone (L1)
DFO	Active comparator	Deferoxamine (DFO) monotherapy Receives: Drug: Deferoxamine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Left Ventricular Ejection Fraction (LVEF).
The primary outcome variable is change in left ventricular ejection fraction (blood ejected from the heart into the body) as measured by MRI from baseline to one year. The unit of primary outcome (left ventricular ejection fraction) is the percent of the blood in left ventricle.
Measured: Baseline to one year

Secondary outcomes (6)

Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*.
Measured: one year
Change in Left Ventricular (LV) Volume From Screening to One Year.
Measured: one year
Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year.
Measured: one year
Change in Holter Monitor Scores From Baseline to One Year.
Measured: one year
Initiation of or Increase in Cardiac Medications
Measured: continuous
Adverse Events
Measured: continous

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2005Apr 2009

First posted22 Jun 2005 (estimated)
Study startJun 2005
Primary completionJul 2008
Study completionApr 2009

Why it stopped: due to low enrollment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cardiovascular DiseasesStudies 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: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00115349
Sponsor's protocol ID: 181
Other IDs: U01HL065260, U01HL065244, U01HL065239, U01HL065238, U01HL065232
Status last verified: Jan 2014
First submitted: 21 Jun 2005
Last updated: 1 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.
PubMed 37975597

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Thalassemia Clinical Research Network - Cardiac L1/DFO Trial
ClinicalTrials.gov ID: NCT00115349
Acronym / sponsor ID: 181
Conditions: Cardiovascular Diseases, Heart Diseases, Beta-Thalassemia
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: due to low enrollment
Enrolment: 20 participants (actual)
Lead sponsor: Carelon ResearchUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Jun 2005
Primary completion: Jul 2008 (actual)
Study completion: Apr 2009 (actual)
First posted: 22 Jun 2005 (estimated)
Results: Posted 14 Jan 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

DESIGN NARRATIVE:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
L1/DFO	Experimental	Drug: Deferoxamine, Drug: Deferiprone (L1)Deferoxamine (DFO) and deferiprone (L1) combination therapy
DFO	Active comparator	Drug: DeferoxamineDeferoxamine (DFO) monotherapy

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Transfusion-dependent beta-thalassemia (eight or more transfusion episodes in the previous year)
Left ventricular ejection fraction by MRI less than or equal to 56% by balanced steady-state free precession (SSFP) or 63% by spoiled gradient recalled echo (SPGR)
Currently on treatment with subcutaneous or intravenous DFO; participants must be willing and able to chelate 7 days per week 12 - 24 hours per day
Serum ferritin greater than 1000 µg/L or ferritin between 500 µg/L and 1000 µg/L and cardiac T2* less than 20 ms

Key exclusion criteria (11 listed)

Pacemaker, severe claustrophobia, or other contraindications to MRI; severe congestive heart failure (New York Heart Association Classification IV); congenital or acquired valvular heart disease significant enough to require surgery or medications
Currently receiving treatment for hepatitis; renal insufficiency defined by a clinically significant abnormal serum creatinine with a calculated creatinine clearance of less than 50 ml/min according to the Cockroft formula
A neutrophil count less than 1.5 x 109/L on two or more occasions at least 4 weeks apart within the past year and not associated with an acute viral illness or a platelet count less than 80 x 109/L on two or more occasions at least 4 weeks apart within the past year
Treatment with L1 or Exjade during the previous 2 weeks or previous adverse experience to L1 requiring suspension
Infection with HIV

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
DeferoxamineAlso: DFODeferoxamine will be given daily for 12-24h/day 7 days a week either subcutaneous or intravenous at up to 50-60 mg/kg/day.	Drug	DFO, L1/DFO
Deferiprone (L1)Also: L1The dose of L1, 75mg/kg in three divided oral doses, is the maximum dose at which toxicity has been tested in prospective trials	Drug	L1/DFO

Primary outcome

Change in Left Ventricular Ejection Fraction (LVEF).
Time frame: Baseline to one year
The primary outcome variable is change in left ventricular ejection fraction (blood ejected from the heart into the body) as measured by MRI from baseline to one year. The unit of primary outcome (left ventricular ejection fraction) is the percent of the blood in left ventricle.

6 secondary outcomes

Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*.
Time frame: one year
Change in Left Ventricular (LV) Volume From Screening to One Year.
Time frame: one year
Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year.
Time frame: one year
Change in Holter Monitor Scores From Baseline to One Year.
Time frame: one year
Initiation of or Increase in Cardiac Medications
Time frame: continuous
Adverse Events
Time frame: continous

Results and safety

Results posted to the registry on 14 Jan 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy	11	0
Deferoxamine (DFO) + Monotherapy	9	0

Primary outcome: Change in Left Ventricular Ejection Fraction (LVEF).

Time frame: Baseline to one year. Least squares mean (Standard Error). Unit: Percent of the blood in left ventricle

Measure	Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy n = 11	Deferoxamine (DFO) + Monotherapy n = 9
Value	7.2 (1.9)	6.3 (3.3)

Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy vs Deferoxamine (DFO) + Monotherapy: p = 0.89, Mixed Models Analysis

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy	6 of 11 (54.5%)	8 of 11 (72.7%)	Not reported
Deferoxamine (DFO) + Monotherapy	3 of 9 (33.3%)	6 of 9 (66.7%)	Not reported

Limitations and caveats (from the sponsor): The study was stopped early by NHLBI when analysis of the interim data confirmed a required sample size of 86 that was not achievable within the required time frame within the participating or planned centres.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37975597Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.

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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.

John Porter, MD principal investigator

University College, London

Patricia J. Giardina, MD study chair

Weill Medical College of Cornell University

Ellis J. Neufeld, MD study chair

Boston Children's Hospital

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Deferoxamine and Deferiprone (L1) in people with Cardiovascular Diseases and Heart Diseases, run by Carelon Research at 6 sites in United States.

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 4 inclusion and 11 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: stopped early, as of the sponsor's last update on 1 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Left Ventricular Ejection Fraction (LVEF). (time frame: Baseline to one year). 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 NCT00115349, which also lists 1 linked publication.

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 1 Mar 2018.