Clinical trial NCT03535532: Unilateral Laparoscopic Adrenalectomy for Resistant Hypertension in Patients With Adrenal Diseases
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Resistant Hypertension
Adrenal Disease
Keywords: resistant hypertension
Adrenal Disease
medical treatment
laparoscopic adrenalectomy
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
First posted: 2018-05-24
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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-functional"and 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.

Eligibility criteria: Inclusion Criteria:

1. 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)
2. Signed the written informed consent.

Exclusion Criteria:

1. 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)
2. Patients who has proceeded unilateral laparoscopic adrenalectomy once;
3. Severe somatic disease such as cancer;
4. Severe cognitive impairment or mental disorder;
5. Participating in other clinical trials.

Primary outcomes:
measure: A composite of end-point events
timeFrame: 3 year
Secondary outcomes:
measure: Major coronary events
timeFrame: 3 years
measure: First occurrence of symptomatic stroke (ischemic or hemorrhagic, fatal or nonfatal)
timeFrame: 3 years
measure: All-cause death
timeFrame: 3 years
measure: Cardiovascular death
timeFrame: 3 years
measure: myocardial infarction
timeFrame: 3 years
measure: Hospitalization for unstable angina
timeFrame: 3 years
measure: Hospitalization for acute decompensated heart failure
timeFrame: 3 years
measure: coronary revascularization (percutaneous coronary intervention [PCI], coronary bypass grafting [CABG])
timeFrame: 3 years
measure: First occurence of diabetes mellitus
timeFrame: 3 years
measure: Decline in cognitive function
timeFrame: 3 years
measure: Decline in renal functio or development of end stage renal disease (ESRD)
timeFrame: 3 years
measure: Major artery function changes
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences, FuWai Hospital
state: Beijing
city: Ji'nan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Ji'ning
country: China
facility: Yunzhou Municiple Hospital
state: Shandong
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jun Cai, MD
role: STUDY_DIRECTOR
References:
citation: Sim JJ, Bhandari SK, Shi J, Reynolds K, Calhoun DA, Kalantar-Zadeh K, Jacobsen SJ. Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and nonresistant hypertension. Kidney Int. 2015 Sep;88(3):622-32. doi: 10.1038/ki.2015.142. Epub 2015 May 6.
citation: Lopez D, Luque-Fernandez MA, Steele A, Adler GK, Turchin A, Vaidya A. "Nonfunctional" Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes: A Cohort Study. Ann Intern Med. 2016 Oct 18;165(8):533-542. doi: 10.7326/M16-0547. Epub 2016 Aug 2.
citation: Xu T, Xia L, Wang X, Zhang X, Zhong S, Qin L, Zhang X, Zhu Y, Shen Z. Effectiveness of partial adrenalectomy for concomitant hypertension in patients with nonfunctional adrenal adenoma. Int Urol Nephrol. 2015 Jan;47(1):59-67. doi: 10.1007/s11255-014-0841-8. Epub 2014 Oct 11.
citation: Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S, Dekkers OM. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016 Aug;175(2):G1-G34. doi: 10.1530/EJE-16-0467.
citation: Denolle T, Chamontin B, Doll G, Fauvel JP, Girerd X, Herpin D, Vaisse B, Villeneuve F, Halimi JM. [Management of resistant hypertension. Expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology]. Presse Med. 2014 Dec;43(12 Pt 1):1325-31. doi: 10.1016/j.lpm.2014.07.016. Epub 2014 Nov 20. French.