Study of Erythropoietin to Treat Anemia Complicating Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine the impact of erythropoietin treatment of anemia on exercise capacity of patients with chronic obstructive pulmonary disease (COPD).

Detailed Description
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The development of anemia in patients with chronic obstructive pulmonary disease (COPD) is now taken as a predictor of increased morbidity and mortality. Preliminary data from patients investigated in our department indicate a negative correlation between anemia severity and 6-minute walking distance. Our working hypothesis is that hemoglobin level correction by erythropoietin therapy will improve the effort capacity of patients with COPD and anemia. Our objective is to conduct a pilot study of the efficacy of darbepoetin alfa. The study will include about 15 patients with COPD recruited at three pulmonology centers based on two selection criteria: COPD stage II or III or IV according to GOLD criteria and hemoglobin level less than 12 g/dL. Effort capacity will be evaluated chiefly by performing a 6-minute walking test and by measuring VO2 at maximum exertion on a bicycle ergometer with increasing loads. Darbepoetin alfa will be given for 2 months. If the hemoglobin increase is less than 1 g/dL after 1 month, the dosage will be increased by 25%. Effort parameters will be measured at baseline and after 1 and 2 months of treatment. Among secondary objectives, we will evaluate functional ergospirometric parameters and laboratory tests for inflammation. Total study duration will not exceed 18 months.

Official Title
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Erythropoietin Treatment of Anemia Complicating Chronic Obstructive Pulmonary Disease: Functional Impact During Exertion

Conditions
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Anemia, Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female aged 40-75 years Diagnosis of a moderate to very severe COPD (stage II, III or IV according to GOLD criteria) A ratio of post-bronchodilator FEV1 to forced vital capacity (FVC) < 70% A FEV1 < 80% of the predicted value Hemoglobin level less than 12 g/dL Peak VO2 less than 80% of predict value and 6-min walk test distance less than 500 meters Exclusion Criteria: Hemorrhagic anemia Iron deficiency anemia (ferritin < 30 ng/ml) Folate and Vitamin B12 deficiency anemia Myelodysplastic Syndrome Chronic disease associated with anemia: renal insufficiency, inflammatory disease, neoplastic disease, left ventricular insufficiency (ejection fraction < 40%) Chronic disease likely to interfere with dyspnea or exercise testing (cardiac insufficiency, neurologic disease, claudication) Acute exacerbation of COPD within the last 4 weeks History of thromboembolic disease Contraindications for cardiopulmonary exercise testing Contraindications for darbepoetin alfa treatment: uncontrolled arterial hypertension or hypersensitivity reaction to darbepoetin alfa Pregnancy or breast-feeding (women of reproductive potential should use adequate birth control measures during the whole duration of study treatment)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Darbepoetin alfa<br>* Dosage form: injection (to store between 2 and 8 °C). Dosage: various dosages are available (10, 15, 20, 30, 40, 50, 60, 80, 100, 150 or 300 µg/ml). Frequency: every week for 2 months: 8 injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure: 6-minute walk distance |  | before treatment; at one month and two months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VO2 max |  | before treatment; at one month and two months | 
| MRC Dyspnea score |  | before treatment; at one month and two months | 
| St. George quality of life score |  | before treatment and at two months of treatment | 
| Inflammation biological parameters |  | before treatment and at two months of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Chronic obstructive Pulmonary Disease, Erythropoietin, 6-minute walk test