A First-in-human Study of HyperQureTM", Laparoscopic Renal Denervation Therapy in Patient With Resistant Hypertension

Inclusion Criteria:

Subjects are deemed eligible for this clinical trial only if they meet all of the following criteria:

1. Male and female patients aged between 19 and 79 years old

2. Resistant hypertensive patients on stable regimen of at least 3 antihypertensivemedications* for at least 4weeks prior Screening1 and those who are willing tocontinue existing antihypertensive medications during run- in period and till 3months after surgery from Screening 1

• Patients on at least 3 antihypertensive medications of different classesincluding diuretics

3. Those who meet the following blood pressure requirements:

[Screening 1]

• Office systolic blood pressure (SBP) ≥ 140 mmHg

• Office diastolic blood pressure (SBP) ≥ 90 mmHg

[Screening 2]

• Office SBP ≥ 140 mmHg

• Office DBP ≥ 90 mmHg

• Daytime ASBP ≥ 135 mmHg

4. Those who have the ability and willingness to provide voluntary and written consentto participate in this clinical trial

Exclusion Criteria:

Subjects cannot be enrolled in the clinical trial if they meet any of the following criteria

1. Those with the following confirmed anatomical findings in the kidney or renal arterythat are unsuitable for renal denervation (assessed based on the results of therenal CT angiography of Screening 2)

• If there is an atheroma or renal artery stent within 5 mm of the renaldenervation site

• Presence of stenosis of 30% or more on all of the blood vessels available forrenal denervation therapy

• When it is deemed impossible to perform denervation on both renal arteriesaccording to the discretion of the investigator

2. Those with a medical history or a history of surgery/procedure that is unsuitablefor renal denervation therapy

• Renal denervation therapy

• Renal artery stenting within 3 months prior to surgery

• Polycystic kidney disease (PKD)

• Atrophic kidney

• Kidney transplant

• Dialysis due to end-stage renal disease

• Any surgery performed on the both kidney

• FMD(Fibromuscular dysplasia)

3. Those with a confirmed comorbidity or a history of surgery/procedure that isunsuitable for posterior retroperitoneal approach required for renal denervationtherapy

• Surgical history using the retroperitoneal approach

• Fibrosis of the retroperitoneal region

• Inflammation of the retroperitoneal region

• Extreme obesity (body mass index (BMI) > 40 kg/m2)

• Risk of elevated intracranial pressure

4. eGFR* < 45 mL/min/1.73 m2

• eGFR calculation formula (MDRD equation) 175 × (sCr)-1.154 × (age)-0.203 × (0.742 if female)

5. Those with type 1 diabetes or uncontrolled type 2 diabetes*

• Uncontrolled type 2 diabetes: HbA1c ≥ 8.0%

• HbA1c will be tested in Screening 2 if the confirmed HbA1c result is from thetest conducted 3 months before Screening 2 or if additional tests are deemednecessary according to the investigator discretion due to a history ofinadequately controlled blood glucose level.

6. Those who receive SGLT2 inhibitors or GLP-1 agonists within 90 days before Screening 1, or those who are expected to require treatment during the clinical trialperiod(but if on continuous medication without changes more than 90days can beenrolled)

7. Those with at least a 20-mmHg decrease in office SBP or at least a 10-mmHg decreasein office DBP accompanied by symptoms, measured within 3 minutes of standing upduring Screening 2(but if orthostatic hypotension is clearly due to Benign ProstaticHyperplasia, subject can be enrolled)

8. Those who are likely to experience safety problems due to blood pressure dropaccording to the discretion of the investigator (e.g., heart valve stenosis,peripheral vascular disease, aortic aneurysm, and high-risk groups for bleeding (thrombocytopenia, hemophilia, severe anemia, etc.)

9. Those who have difficulty in measuring blood pressure accurately according to thediscretion of the investigator (e.g., if the circumference of the upper arm islarger than the cuff size of the blood pressure monitor, those with arrhythmia,etc.)

10. Those who have secondary hypertension or are receiving sympathomimetic drugs thataffect hypertension

11. Those with a history of the following cardiovascular diseases or accompanyingdiseases

• Myocardial infarction occurring within 3 months prior to Screening 1

• Stable/Unstable angina occurring within 3 months prior to Screening 1

• Heart failure(NYHA classification III~IV) within 3 months prior to Screening 1

• Transient ischemic attack

• Cerebrovascular seizures (e.g., subarachnoid hemorrhage, cerebral embolism,etc.)

• Atrial fibrillation (except for those who have confirmed sinus rhythm afterundergoing surgery, such as catheterization for the treatment of atrialfibrillation)

12. Those with primary pulmonary hypertension

13. Those with confirmed bleeding diathesis, coagulation disorder, or refusal to receivetransfusions

14. Those with a history of peptic ulcer disease or gastrointestinal bleeding within 6months prior to Screening 1

15. Those who are chronically on oxygen-assisted or mechanical ventilation (e.g., CPAP,BiPAP) (however, usage due to sleep apnea is exempted)

16. Those who have taken non-steroidal anti-inflammatory drugs (NSAIDs) twice or moreper week for pain control within 1 month prior to Screening 2

17. Those with a history of contraindications to the use of contrast agents,anaphylactic reactions, or uncontrolled allergic reactions

18. Those receiving antiretroviral drug therapy due to HIV infection (except when thereis a documented history of hypertension prior to initiation of antiretroviral drugtherapy)

19. Those with the following confirmed drug administration history in relation tonarcotic drugs:

• A history of abuse of narcotic drugs

• Those who use methadone

• Those who have used narcotic drugs twice or more within 1 month prior toScreening 1

20. Those with drug or alcohol dependence that has not been cured at the time ofScreening 1, and who lack the ability or are unable to understand and follow theinstructions required in this clinical trial

21. Those who are scheduled to undergo a surgery/procedure that is expected to affectthe efficacy and safety of this clinical trial according to the discretion of theinvestigator

22. Night shift workers

23. Those who have received other investigational products or investigational medicaldevices within 4 weeks prior to Screening 1 (however, such patients may be enrolledif such products of devises do not affect the efficacy and safety assessment of thisclinical trial according to the discretion of the investigator)

24. Women who are pregnant, lactating, or plan to become pregnant during the period ofthe clinical trial

25. Other subjects who are deemed ineligible to participate in this clinical trialaccording to the investigator's discretion