Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity
Summary
The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events, to elucidate whether differences in this ratio might have a positive or negative predictive value in diagnosing atorvastatin muscle toxicity.
Description
The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events, to elucidate whether differences in this ratio might have a positive or negative predictive value in diagnosing atorvastatin muscle toxicity. If this is shown, measurements of atorvastatin metabolites from patients experiencing muscle adverse events might be a valuable diagnostic tool to diagnose myopathy associated with statin treatment. The primary endpoint cut off level for present myotoxicity has been set to a ratio of p-hydroxyatorvastatin /atorvastatin of 0.15 from the previously performed pilot study (Unpublished data, Herman M et al). Values at or above this ratio will be considered as clinical significant indicia of statin related myopathy.
Secondary objectives include descriptively investigation of drug to metabolite cut off ratio for atorvastatin lactone/atorvastatin. Whether other cut off values, both for p-hydroxyatorvastatin as well as for atorvastatin lactone, give more precise identification of patients that are experiencing statin related myopathy compared to controls will also be investigated.
Explorative objectives of the study are to investigate possible in vitro phenotypic differences in isolated muscle cells from patients experiencing muscle toxicity compared to patients not experiencing muscle toxicity. If there are genetic differences between patients experiencing myotoxicity and those not, this difference is likely to show as phenotypic differences in in vitro studies of isolated muscle cells. If such phenotypic differences are present in vitro possible mechanistic causes will be further investigated.
Study Design
Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Investigator), Primary Purpose: Diagnostic
Conditions
Myotoxicity of Atorvastatin Treatment
Intervention
Atorvastatin
Location
Rikshospitalet-Radiumhospitalet HF, Lipid clinic
Oslo
Norway
0027
Status
Completed
Source
University of Oslo School of Pharmacy
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00414531
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Withholding Treatment
Withholding or withdrawal of a particular treatment or treatments, often (but not necessarily) life-prolonging treatment, from a patient or from a research subject as part of a research protocol. The concept is differentiated from REFUSAL TO TREAT, where the emphasis is on the health professional's or health facility's refusal to treat a patient or group of patients when the patient or the patient's representative requests treatment. Withholding of life-prolonging treatment is usually indexed only with EUTHANASIA, PASSIVE, unless the distinction between withholding and withdrawing treatment, or the issue of withholding palliative rather than curative treatment, is discussed.
Khellin
A vasodilator that also has bronchodilatory action. It has been employed in the treatment of angina pectoris, in the treatment of asthma, and in conjunction with ultraviolet light A, has been tried in the treatment of vitiligo. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1024)
Directly Observed Therapy
A treatment method in which patients are under direct observation when they take their medication or receive their treatment. This method is designed to reduce the risk of treatment interruption and to ensure patient compliance.
Fluoxymesterone
An anabolic steroid that has been used in the treatment of male HYPOGONADISM, delayed puberty in males, and in the treatment of breast neoplasms in women.
Reflexotherapy
Treatment of some morbid condition by producing a reflex action, as in the household treatment of nosebleed by a piece of ice applied to the cervical spine. (Stedman, 27th ed)
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