A Randomized, Open-label Therapeutic Trial Evaluating the Efficacy and Safety of Neridronate (Nerixia®) in the Treatment of Osteoporosis in Patients With Thalassemia Major and Severe Thalassemia Intermedia.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 8
研究概览
简要总结
An Italian Multicentric randomized, open-label therapeutic trial evaluating the efficacy and safety of Neridronate in the treatment of Osteoporosis in patients with Thalassemia Major and Severe Thalassemia Intermedia.
Efficacy and safety of the drug will be evaluated measuring at every visit this parameters:
- haematological: Haemochrome
- blood chemistry: creatinine, BUN, AST, ALT, Ca, P, proteins electrophoresis, total proteins.
The prevalence of ectopic calcification and pseudoxantoma elasticum (PXE)-like syndrome and their follow-up will be evaluated at the beginning of the study vs 24 months through physical examination, abdominal echography and fundus oculi examination.
During the trial other known risks factors for osteoporosis will be recorded, including prevalence and incidence of bone fractures and, if executed, Polimorphisms COLIA1.
At the beginning of the study and at months 12 and 24 morphometry DXA will be performed to evaluate of the presence of bone deformities.
Furthermore data regarding QOL and symptom pain will be evaluated trough administration of scale SF-36.
At 12 months an intratrial analisis will be performed on efficacy and safety parameters in order to introduce possible amendments to the study design and to decide the prosecution of the trial
During the trial all adverse events will be recorded
详细描述
Aim of the Study At present, due to the global therapeutic approach, the prognosis of Thalassemia Major and Severe Thalassemia Intermedia is open-ended. Regular transfusional regimens from childhood and early iron chelation therapy prevent bone deformities that in the past characterized this disease even though according to several authors a high percentage of patients suffers from osteopenia-osteoporosis. This persistent complication may be explained by one or more coexistent factors such as anaemia, genetic factors, sex hormones involved in the bone metabolism, iron and chelation therapy, hypothiroidism, low or subnormal concentrations of serum vitamin D, etc.
Pain resulted to be the only parameter that may be considered to distinguish patients with Thalassemia Major from healthy patients of the same age through a survey about Quality of Life performed in the Center of Genoa. More frequently pain is localized in the lumbar vertebrae, it is often described with invalidant pictures and it has to be referred to osteoporosis of vertebral bodies.
The incidence of spontaneous fractures observed in the specialistic centers treating these pathologies is increasing.
Thalassemia Intermedia is an eterogeneous clinical entity including a wide range of phenotypes from mild to severe forms. In the mild forms hemoglobin levels range between 8-9 g/dl, which is stable without the need for regular transfusion therapy unless an intercurrent episode aggravates anemia; no expansion of the bone marrow is observed. By contrast, there are forms in which anemia is persistently more severe (6.5- 7.5 g/dl) with marked ineffective erythropoiesis. In these cases, especially when the diagnosis is made in childhood, patients should receive a transfusional regimen similar to Major forms with similar complications such as osteoporosis.
For these reasons in patients affected with Severe Thalassemia Intermedia and with Thalassemia Major prevention and early diagnosis of osteoporosis are important as well as treatment of the established disease in order both to improve quality of life and life expectancy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients presenting BMD Z score <-2 at the level of the femoral neck or of the lumbar column Regular transfusional regimen in order to mantain pre-transfusional Hb values >9 g/dl.
- •Written informed consent by the patient
排除标准
- •Entravenous administration of bisphosphonates within the past 2 years
- •Administration of di bisphosphonates per os, unless wash out as it follows:
- •1 year if >8 weeks <48 weeks 6 months if > 2 weeks and <8 weeks Hypoparathyroidism Thalassemia Intermedia if not regularly transfused Pregnancy and breast feeding Impaired renal function (creat. > 1.5 mg/dl) Neoplastic disease Patients with mean levels of alanine aminotransferase ALT > 300 U/l and patients with variations of AST or AST of 300% within the year before randomization. (At least 4 misurations over 12 months) Systemic cardiovascular, renal, hepatic disease etc. which would prevent the patient from undergoing study treatment Known hypersensibility to bisphosphonates. History of non compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative.
研究组 & 干预措施
Neridronato
Thalassemia Major or Severe Thalassemia Intermedia
干预措施: Neridronate (Drug)
研究者
Dr. Gian Luca Forni
MD
Ente Ospedaliero Ospedali Galliera