Unilateral Laparoscopic Adrenalectomy for Resistant Hypertension in Patients With Adrenal Diseases

Study Overview
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Brief Summary
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ULARH is a 2-arm, prospective, open-labeled, multi-center randomized clinical trial.The purpose of this study is to compare the effectiveness of medical treatment and unilateral laparoscopic adrenalectomy for resistant hypertension in patients diagnosed with adrenal disease based on imaging tools.Relative ratio of end-point events occurence in three years is considered as primary outcome. Furthermore, we will exploit clinical factors which could indicate a favorable outcome in participants who accepted surgical treatment in this study.

Detailed Description
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Resistant hypertension is a clinical condition characterized by the presence of BP values above the recommended limits of the reference values(BP>140/90 mmHg in hypertensive patients), despite the adherence to appropriate life style changes and to a drug therapy of at least three classes of drugs, one of which is represented by a diuretic, in adequate doses. Several small-sample studies suggest the prevalence of resistant hypertension is about 5-30% in Chinese population. Uncontrolled blood pressure elevation attributes to a higher incidence of stroke, heart failure, chronic renal disease, dementia and cardiovascular deaths. Improving the management of resistant hypertension is a constantly tricky problem in hypertension clinical practice. Compared with patients whose blood pressure level are more easily to get controlled, patients diagnosed with resistant hypertension presented a higher risk of adrenal anomaly when screened by imaging tools. Current clinical practice guidance recommend unilateral laparoscopic adrenalectomy as a preferable treatment merely for adrenal incidentalomas with over hormone secreting like cortisol or aldosterone, or a high likelihood of malignance. Among patients who meet above surgery indication, the ratio of cure for hypertension varies from approximately 30 to 80%. However, in recent years, there are growing evidence showed that hypertensive patients diagnosed with adrenal disease based on imaging tools also gain much benefit from adrenalectomy even if there is no evidently abnormal hormone secretion. Last year, a prospective cohort study published on <Ann Intern Med> suggested that nonfunctional adrenal tumors associate with increased diabetes risk. These studies prompt a re-assessment of the classification of benign adrenal tumors as non-functionaland their potential damage. In a retrospective study conducted by our group in early period to evaluate the effect of surgery treatment in resistant hypertensive patients, we found one third of resistant hypertensive patients were cured as well as another one third get improved after unilateral laparoscopic adrenalectomy. Thus, we designed this study, expecting a further and more detailed perception of the relationship between resistant hypertension and adrenal anomaly.

Official Title
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Effectiveness Comparison of Medical Treatment and Unilateral Laparoscopic Adrenalectomy for Resistant Hypertension in Patients Concomitant With Adrenal Diseases: A Prospective, Multi-Center, Open-Labeled, Randomized Clinical Trial.

Conditions
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Adrenal Disease, Resistant Hypertension

Intervention / Treatment
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* Procedure: unilateral laparoscopic adrenalectomy
* Drug: standard medical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resistant hypertensive patients diagnosed with adrenal disease based on imaging tools (resistant hypertension defined as the presence of BP values above the recommended limits of the reference values(BP>140/90 mmHg),despite the adherence to appropriate life style changes and to a drug therapy of at least three classes of drugs for at least one month, one of which is represented by a diuretic, in adequate doses) Signed the written informed consent. Exclusion Criteria: Patients with surgical contraindication;(Performed coronary revascularization (PCI or CABG) within the previous 6 months; Cerebral hemorrhagic stroke within the previous 3 months, or new onset cerebral infarction within the latest 2 weeks;Severe heart failure or kidney disfunction within the previous 6 months) Patients who has proceeded unilateral laparoscopic adrenalectomy once; Severe somatic disease such as cancer; Severe cognitive impairment or mental disorder; Participating in other clinical trials.
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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: resistant hypertensive patients diagnosed with adrenal diseases based on imaging tools will be randomly allocated into unilateral laparoscopic adrenalectomy group and standard medical treatment group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: unilateral laparoscopic adrenalectomy<br>subjects allocated in this group will be given unilateral laparoscopic adrenalectomy as treatment. | Procedure: unilateral laparoscopic adrenalectomy<br>* unilateral laparoscopic adrenalectomy is a kind of minimally invasive surgery commonly operated in patients diagnosed with adrenal diseases with a high likelihood of malignance or surplus hormone secretion.<br>* Other names: standard medical treatment;|
| Active Comparator: standard medical treatment<br>subjects allocated in standard medical treatment group will be given conservative medicine treatment. | Drug: standard medical treatment<br>* standard medical treatment: detailed medicine strategy chosen for each patient will be associated with their own conditions based on current guidance recommendations.<br>* Other names: unilateral laparoscopic adrenalectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of end-point events | A composite end-point comprised of myocardial infarction(MI), congestive heart failure, cerebrovascular event, end stage renal disease, death. | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major coronary events | Major coronary events comprised of myocardial infarction (MI), hospitalization for unstable angina or acute decompensated heart failure, coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]), and death from cardiovascular causes. | 3 years | 
| First occurrence of symptomatic stroke (ischemic or hemorrhagic, fatal or nonfatal) | First occurrence of symptomatic stroke (ischemic or hemorrhagic, fatal or nonfatal) | 3 years | 
| All-cause death | All-cause death | 3 years | 
| Cardiovascular death | Cardiovascular death | 3 years | 
| myocardial infarction | myocardial infarction | 3 years | 
| Hospitalization for unstable angina | Hospitalization for unstable angina | 3 years | 
| Hospitalization for acute decompensated heart failure | Hospitalization for acute decompensated heart failure | 3 years | 
| coronary revascularization (percutaneous coronary intervention [PCI], coronary bypass grafting [CABG]) | coronary revascularization (percutaneous coronary intervention [PCI], coronary bypass grafting [CABG]) | 3 years | 
| First occurence of diabetes mellitus | First occurence of diabetes mellitus | 3 years | 
| Decline in cognitive function | Decline in cognitive function includes sensory disturbance, memory disorders and thinking disorders, which is assessed by mini-mental state examination (MMSE) | 3 years | 
| Decline in renal functio or development of end stage renal disease (ESRD) | Decline in renal function is assessed by any of the following: (1) For patients with chronic kidney disease (eGFR<60 ml per minute per 1.73 m2) at baseline, the renal outcome was a composite of a decrease in the eGFR of 50% or more (confirmed by a subsequent laboratory test) or the development of EDRD requiring long-term dialysis or kidney transplantation; or (2) For participants without chronic kidney disease at baseline, the renal outcome was defined by a decreased in the eGFR of 30% or more to a value of less than 60 ml per minute per 1.73 m2. | 3 years | 
| Major artery function changes | Major artery function changes are assessed by a composite of decrease in the ankle branchial index [ABI], brachial-ankle pulse wave velocity(baPWV),or brachial artery flow-mediated dilation [FMD]. ABI and baPWV, well-established non-invasive techniques fr evaluating obstruction and stiffness of peripheral artery respectively, are considered for the purposes of cardiovascular risk assessment. ABI is the ratio of average systolic blood pressure measured in brachial/ankle, and an ABI between and including 0.9 and 1.2 is considered normal, while a lesser than 0.9 indicates arterial disease. The unit measure of baPWV value is cm per second. FMD serves as an index of nitric oxide (NO)-mediated endothelium-dependent vasodialator function in humans and is regarded as a surrogate marker of cardiovascular disease. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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resistant hypertension, Adrenal Disease, medical treatment, laparoscopic adrenalectomy