Clinical trial NCT00000595: Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia (Iron-Loading)
Beta-Thalassemia
Hematologic Diseases
Hemoglobinopathies
Thalassemia
Iron Overload
Hemochromatosis
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 1999-10-28
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine whether deferoxamine prevented the complications of transfusional iron overload.

Detailed description: BACKGROUND:

The prognosis of congenital or long-term anemia was formerly limited by the complications of blood transfusion, splenectomy, or infection, problems now largely overcome by sophisticated clinical care. Lifespan is now determined by the rate of myocardial iron deposition, with death occurring from cardiac failure or arrhythmia, usually between the ages of 15 and 25. Endocrine complications and hepatic enlargement are also evident by this age. Deferoxamine increases urinary iron excretion and is the only chelator currently available for chronic administration. Daily administration of deferoxamine results in negative iron balance in most patients by the age of 10; this study was designed to determine whether the onset of cardiac complications was delayed and life prolonged by iron removal.

This trial began in 1978. Its forerunner was a study involving both deferoxamine and ascorbic acid. Although ascorbic acid promotes iron removal, its administration was followed by cardiac deterioration in several patients. In this study, patients receiving subcutaneous deferoxamine were randomized to receive either ascorbic acid or placebo, thereby providing a controlled test of this agent in treatment of iron overload. Sixty-five patients with homozygous beta-thalassemia participated in the long-term chelation trial. Of these, 49 were randomized to the ascorbic acid trial.

Several noninvasive techniques have been developed to evaluate organ function in iron-overloaded patients, thereby facilitating the assessment of chelation therapy. These techniques included chest x-rays, electrocardiograms, echocardiograms, and 24-hour Holter monitoring to assess cardiac function. Liver function was evaluated by standard liver function tests, CAT scan, and live biopsy. During the last six years of the study, hepatic iron stores were measured magnetically with a dual channel superconducting quantum-interference susceptomer. Endocrine function was also assessed by standard tests.

DESIGN NARRATIVE:

All patients received subcutaneous deferoxamine and iron removal was determined by measurement of serum ferritin and periodic non-invasive measurements of liver iron concentration. Clinical status was evaluated by non-invasive testing of cardiac and endocrine function.

The study completion date listed in this record was inferred from the last publication listed in the Citations section of this study record.

Eligibility criteria: Males and females, 5 years or older, with transfusional hemochromatosis.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Laboratory of Hematology, NHLBI
name: Neal Young
References:
citation: Nienhuis AW, Griffith P, Strawczynski H, Henry W, Borer J, Leon M, Anderson WF. Evaluation of cardiac function in patients with thalassemia major. Ann N Y Acad Sci. 1980;344:384-96. doi: 10.1111/j.1749-6632.1980.tb33677.x.
citation: Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med. 1994 Sep 1;331(9):567-73. doi: 10.1056/NEJM199409013310902.