NCT06414746已完成不适用
A Multicenter Observational Retrospective-prospective Study of Prevalence, Clinical Characteristics of Hereditary Transthyretin Amyloidosis Polyneuropathy in Russian Patients Undergoing Surgery for CTS in Real Clinical Practice
适应症
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 721
- 试验地点
- 14
- 主要终点
- To define the prevalence of ATTR PN in patients diagnosed with CTS and having bilateral involvement in routine clinical practice in the Russian Federation.
研究概览
简要总结
This is a multicenter observational study consisting of retrospective and prospective phases. The retrospective phase will entail secondary data collection from electronic or paper medical records of patients who underwent surgery for CTS to assess their probability of having ATTR PN.
详细描述
ATTR PN is a genotypically, phenotypically and geographically variable disease with a poor prognosis, albeit available disease-modifying drugs can change the disease trajectory. Thus country-specific epidemiologic data collection and identification of early stage PN, including previously misdiagnosed patients, is crucial to improve outcomes and quality of life. However, no observational studies on the epidemiology of ATTR PN in the whole Russian population, or in patients with CTS, have been performed.
Therefore, there is a need to conduct a large-scale observational study to determine the prevalence of ATTR PN in Russia, obtain information on patients' clinical characteristics, and determine their medical needs.
The approaches to diagnosis of ATTR PN in Russia over the past few years have been characterized by the use of heterogenous methods, partially explained by the lack of availability of molecular genetic testing, which is essential to diagnose the presence of pathogenic mutation in patients with hereditary ATTR PN. Thus, recent introduction of such tests into routine clinical practice may allow to assess reliable epidemiologic data including estimation of true ATTR PN prevalence among patients with CTS, which can often be the first manifestation of the disease. Earlier recognition, in turn, may lead to timely treatment initiation and change in the prognostic outlook of ATTR PN patients.
In order to assess the prevalence of ATTR PN in patients undergoing surgery for CTS in Russia this study will retrospectively include patients with the diagnosis of CTS undergoing surgery between the 1st January 2021 and the 1st September 2024. Suspicion of ATTR PN will be assessed in each case, and diagnostic tests (comprehensive neurological examination including nerve conduction study (NCS) combined with molecular genetic testing) to confirm or exclude the disease will be conducted prospectively in eligible patients. In addition to that, clinical features, concomitant manifestations, and diagnosed genotypes will be analyzed to examine characteristic ATTR PN patient profiles in the Russian Federation.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
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
- •for the retrospective phase are:
- •Patients with the established diagnosis of CTS.
- •Bilateral involvement of carpal tunnel established between the 1st January 2021 and the 31st December 2024 (both patients who underwent CTS surgical intervention and without it are enrolled).
- •Age ≥ 18 years at the time of CTS diagnosis.
- •Provided written informed consent for the prospective phase of the study (including molecular genetic testing).
- •Presence of ≥1 of the following features (red flags):
- •a. CIDP or polyneuropathy of unknown etiology in the family history; b. Spinal canal stenosis of the lumbar region; c. Autonomic dysfunction, defined by the presence of ≥1 of the following symptoms - i. Gastrointestinal complaints (constipation, chronic diarrhea, or both); ii. Erectile dysfunction; iii. Orthostatic hypotension; d. Gait disorders; e. Sweating disorders, anhidrosis. f. Paresthesia and burning of the skin of the distal extremities g. Distal symmetrical paresis h. Hypotrophy and hypotension of limb muscles, areflexia i. Biceps tendon rupture j. Aortic valve stenosis k. Diagnosis of HFpEF
- •l. Unexplained weight loss ≥5 kilos at any timepoint since the onset of symptoms of CTS; m. Left ventricular hypertrophy (based on electro- or echocardiographic criteria documented in the patient's medical record); n. Heart rhythm disorders; o. Renal abnormalities, defined by ≥1 of the following features - i. Documented diagnosis of chronic kidney disease (CKD); ii. Decreased estimated glomerular filtration rate (eGFR <60 mL/min/1.73m2); iii. Increased serum creatinine (SCr) above reference range of the local laboratory; iv. Albuminuria (≥30 mg/g of creatinine or ≥30 mg/24h); v. Proteinuria (according to urinalysis results); p. Ophthalmology disorder defined by ≥1 of the following features - i. Vitreous body inclusions (opacification); ii. Glaucoma; iii. Pupillary disorders; iv. Vitrectomy
- •Absence of previously established ATTR PN diagnosis (ICD-10 code Е85.1, "Neuropathic hereditary familial amyloidosis").
排除标准
- •Participation in any interventional trial within the period since identification of bilateral involvement of carpal tunnel until the end of current study.
- •The following criteria apply for non-inclusion of patients into the prospective part of the study:
- •Previously performed TTR genetic testing;
- •Verified B12 deficiency;
- •History of alcohol abuse according to the patient's medical record.
结局指标
主要结局
To define the prevalence of ATTR PN in patients diagnosed with CTS and having bilateral involvement in routine clinical practice in the Russian Federation.
时间窗: Up to 12 months
In order to achieve primary objective, the proportion of patients with confirmed diagnosis of ATTR PN (presence of TTR gene mutation according to the results of molecular genetic testing and clinical symptoms and/or signs of polyneuropathy) among those diagnosed with CTS and having bilateral involvement will be calculated.
次要结局
- To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at the onset of CTS symptoms(up to 12 months)
- To assess general demographic characteristics of patients with ATTR PN in Russia: Mean age (years) at the onset of polyneuropathy symptoms(up to 12 months)
- to assess general demographic characteristics of patients with ATTR PN in Russia: Proportion of patients with late (>50 years) diagnosis of ATTR PN(up to 12 months)
- to assess general demographic characteristics of patients with ATTR PN in Russia: Mean age (years) at the time of CTS surgery(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Number and proportion of patients with specific characteristics of the first and repeat CTS surgery(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients with CTS recurrence after surgery(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients undergoing repeat surgery for CTS after the index operation(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients with PN progression after surgery(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Proportion of patients with different number of red flags:(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Mean age (years) at ATTR PN diagnosis(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of women and men(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Mean body mass index (BMI) and proportion of patients with different BMI dimensions at the time of CTS diagnosis and at Visit 1:(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients with a history of unexplained weight loss (≥5 kg) at any point since CTS diagnosis(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Mean and median time from CTS symptom onset (months) to ATTR PN diagnosis(up to 12 months)
- To assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Median number of physicians seen since symptom onset before the correct ATTR PN diagnosis(up to 12 months)
- To assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Median number of hospitalizations for PN before the correct ATTR PN diagnosis(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Number and proportion of patients with previously established incorrect diagnosis according to medical records, specifically with:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN: Proportion of patients with family history of neuropathic disease(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN: Proportion of patients with specific peripheral neurological manifestations:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN: Proportion of patients with specific Polyneuropathy Disability (PND) classes:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Proportion of patients with specific distribution of polyneuropathy symptoms:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with autonomic neurological manifestations, including specifically:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities- Number and proportion of patients taking specific groups of cardiovascular medications at the time of CTS diagnosis and at the time of prospective visit:(up to 12 months)
- Number of patients taking specific groups of cardiovascular medications at the time of CTS surgery and at the time of prospective visit:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with concomitant ophthalmologic manifestations, including specifically(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with concomitant musculoskeletal manifestations, including specifically:(up to 12 months)
- Mean and median serum NT-proBNP (pg/ml) concentration(up to 12 months)
- Proportion of patients with laboratory confirmed paraproteinemia(up to 12 months)
- Mean and median urine albumin-creatinine ratio (UACR, mg/g of creatinine)(up to 12 months)
- Proportion of patients with diagnosed CKD, including specifically(up to 12 months)
- Number of patients with concomitant renal dysfunction, including specifically(up to 12 months)
- Number of patients with confirmed length-dependent peripheral sensory-motor neuropathy based on NCS results(up to 12 months)
- Mean and median measured peripheral sensory nerve conduction velocities(up to 12 months)
- Number of patients with reduced peripheral sensory nerve conduction velocity at ≥1 site(up to 12 months)
- Mean and median measured peripheral motor nerve conduction velocities(up to 12 months)
- Number of patients with reduced motor sensory nerve conduction velocity at ≥1 site(up to 12 months)
- Mean and median measured sensory action potential (SAP) amplitudes(up to 12 months)
- Number of patients with reduced/absent SAP amplitude at ≥1 site(up to 12 months)
- Number of patients with reduced/absent pCMAP amplitude at ≥1 site(up to 12 months)
- Mean and median measured distal compound muscle action potential (dCMAP) amplitudes(up to 12 months)
- Mean and median measured proximal compound muscle action potential (pCMAP) amplitudes(up to 12 months)
- Number of patients with reduced/absent dCMAP amplitude at ≥1 site(up to 12 months)
- Proportion of patients with each score by each parameter of neurological examination(up to 12 months)
- Number of patients in the specific categories of the modified Rankin scale(up to 12 months)
- Proportion of patients with specific number of points according to Inflammatory Neuropathy Cause and Treatment (INCAT) upper extremity scale(up to 12 months)
- Median number of points according to INCAT upper extremity scale(up to 12 months)
- Proportion of patients with specific number of points according to INCAT lower extremity scale(up to 12 months)
- Median number of points according to INCAT lower extremity scale(up to 12 months)
- Mean and median number of points according to combined clinical and electrophysiological score(up to 12 months)
- To describe data on the results of genetic testing for ATTR in CTS patients undergoing surgery:Number and proportion of patients with specific TTR gene mutations(up to 12 months)
- to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Proportion of patients with previously established incorrect diagnosis according to medical records, specifically with:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with autonomic neurological manifestations, including specifically:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with concomitant cardiac manifestations, including specifically:(up to 12 months)
- proportion of patients taking specific groups of cardiovascular medications at the time of CTS surgery and at the time of prospective visit:(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with concomitant ophthalmologic manifestations, including specifically(up to 12 months)
- To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with concomitant musculoskeletal manifestations, including specifically:(up to 12 months)
- proportion of patients with concomitant renal dysfunction, including specifically(up to 12 months)
- proportion of patients with confirmed length-dependent peripheral sensory-motor neuropathy based on NCS results(up to 12 months)
- proportion of patients with reduced peripheral sensory nerve conduction velocity at ≥1 site(up to 12 months)
- proportion of patients with reduced motor sensory nerve conduction velocity at ≥1 site(up to 12 months)
- proportion of patients with reduced/absent SAP amplitude at ≥1 site(up to 12 months)
- proportion of patients with reduced/absent dCMAP amplitude at ≥1 site(up to 12 months)
- proportion of patients with reduced/absent pCMAP amplitude at ≥1 site(up to 12 months)
- proportion of patients in the specific categories of the modified Rankin scale(up to 12 months)
- To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at the primary CTS diagnosis(up to 12 months)
- To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at the identification of bilateral involvement(up to 12 months)
- To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at ATTR PN diagnosis(up to 12 months)
- To assess general demographic characteristics of patients with ATTR PN in Russia -Proportion of patients underwent CTS surgery (i.e. at least one surgery)(up to 12 months)
研究者
研究点 (14)
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