Radiofrequency Ablation Versus Adrenalectomy for Adenoma in Patients With Primary Aldosteronism and Hypertension

N/ANot Yet RecruitingNCT07470580

University Hospital, Toulouse134 enrolled

Overview

Primary aldosteronism (PA) is characterized by hypertension, frequent hypokalaemia, and an inappropriately high aldosterone-to-renin ratio (ARR). Aldosterone-producing adenoma (APA or Conn syndrome) is one of the main causes of primary aldosteronism. Laparoscopic (LA) total-adrenalectomy or adenoma selective is an option to normalize or at least improve blood pressure (BP) control, hypokalaemia, and normalize the ARR. However, the reported result of surgery is around 50% of clinical cure rate with an overall complication rate of 5 to 14% whereas hormonal success reached around 95%. More recently, radiofrequency ablation (RFA) has been used for patients with primary aldosteronism and unilateral adenoma. Investigator Team assume that treatment of unilateral PA by RFA could achieve similar efficacy to treatment by LA, with potentially less adverse events, and could be a more cost-efficient procedure.

Primary aldosteronism (PA) is characterized by hypertension, frequent hypokalaemia, and an inappropriately high aldosterone-to-renin ratio (ARR). Aldosterone-producing adenoma (APA or Conn syndrome) is one of the main causes of PA. Medical therapy or adrenalectomy are the 2 options to be considered. Laparoscopic adrenalectomy (LA) has been reported to be cost-effective compared with lifelong oral administration alone in unilateral PA. Therefore, LA is the gold standard for unilateral PA to normalize or at least improve blood pressure (BP) control, hypokalaemia, and normalize the ARR. However, the reported result of surgery is around 50% of BP control with an overall complication rate of 5 to 14%. More recently, radiofrequency ablation (RFA) has been used for patients with APA with an hormonal success obtained in 92% of patients treated by umbrella-shaped needle . RFA for hypertensive patients with APA seems to be an emerging promising alternative to surgery. . Investigator team anticipate that radiofrequency allows a hormonal success of the same order than with adrenalectomy (around 95%), with simpler follow-up than surgery. The main objective of the study is to test the non-inferiority of radiofrequency ablation compared to adrenalectomy, among hypertensive patients with primary aldosteronism and unilateral adrenal adenoma in order to normalize hormonal endpoints at 3 months of follow-up. Cost-effectiveness and cost-utility analysis will be conducted to assess the efficiency of radiofrequency in the frame of the project.

Study Type

INTERVENTIONAL

Allocation

Interventions

RFA -radiofrequency ablationPROCEDURE

Under real-time multidetector CT-guidance, the patients will be put in either prone or lateral decubitus position to choose for the optimal access route for RFA needle electrode. Under multidetector CT guidance, patients would be treated with regard to optimal RFA needle access route with a hydrodissection or aero dissection if necessary. 2 types of generator (Boston Scientific RF 3000, and Ablatech Amica) and of needle electrodes (Leveen-type extendable, Ablatech) will be used according to the routine care of the centers

AdrenalectomyPROCEDURE

Adrenalectomy may be performed using a laparoscopic or open approach. In either approach, the gland may be approached transabdominally or retroperitoneally. The choice of surgical approach depends on the size and nature of the lesion, the patient's general characteristics and the expertise of the surgeon. Actually, laparoscopic adrenalectomy is considered as the gold standard treatment for the selected patients

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient over 18 years of age * Hypertension confirmed into the previous 9 months by ABPM 24h SBP/DBP \>130 and/or/80 mmHg and/or diurnal SBP/DBP \> 135 and/or 85 mmHg and/or nocturnal SBP/DBP \>120 and/or 70 mmHg with or without antihypertensive treatment * Diagnosis of primary aldosteronism confirmed by hormonal assays no more than 1 year before inclusion * Presence of a unilateral adrenal nodule \<4 cm considered suggestive of a Conn's adenoma on an prior adrenal CT or MRI scan, no more than 1 year before inclusion * Adrenal venous sampling if age \> 35 years (and according to investigator decision if age \<35 years) to look for a lateralization of secretion: cannulation was successful when adrenal/peripheral venous cortisol gradients\>2 and lateralization was assessed by comparison of right and left adrenal venous aldosterone/cortisol ratios with a cut off value\>4 ipsilateral to the nod side to define a positive lateralization of secretion (2) no more than 1 year before inclusion * nodule accessible to RFA according to the judgement of the interventional radiologist performing radiofrequency before randomisation * nodule accessible to surgery * patient willing to return for 6-month follow-up * adult patient able to read the information sheet and give consent to take part in the study * Patients affiliated to the French Health Insurance Exclusion Criteria: * a negative lateralization of secretion on adrenal venous sampling * presence of bilateral adrenal tumours * contralateral or bilateral macronodular adrenal hyperplasia * no documented primary aldosteronism * Cushing's syndrome or pheochromocytoma * adrenal tumour \> 4 cm * refusal to perform adrenal catheterisation if age \> 35 years * double anti-platelet aggregation, coagulation disorders or patients treated with anticoagulant treatment that cannot be stopped * contraindication to anaesthesia * excessive proximity to sensitive adjacent organs * patient who has had a heart attack or stroke within the last 6 months * allergy to iodine * renal insufficiency defined as a clearance of \<30 ml/min * refusal to undergo radiofrequency ablation or adrenal surgery * minors and patients under guardianship, curatorship or safeguard of justice * Inability to speak, read or write French fluently * patients who refuse follow-up * pregnant women or women wishing to become pregnant in the short term; breast-feeding * person taking part or having taken part in other interventional research in the previous 6 months * any other relevant exclusion criteria as determined by the investigator

Outcomes

Primary Outcomes

aldosterone-to-renin ratio (ARR) after 15min in the sitting position

aldosterone-to-renin ratio (ARR) after 15 min in the sitting position. Following the recommendations given by Douillard et al (15), normalisation of the ARR will be defined (according to the measurement method) using: * a cut-off value of the ARR of 23 (plasma aldosterone in pg/mL and direct renin in mIU/l) or 64 (plasma aldosterone in pmol/L and direct renin in mIU/l) * a cut-off value of the ARR of 300 (plasma aldosterone in pg/mL and PRA in ng/mL/h), or 830 (plasma aldosterone in pmol/L and PRA in ng/mL/h), or 25 (plasma aldosterone in pg/mL and PRA in pmol/L/min), or 70 (plasma aldosterone in pmol/l and PRA in pmol/L/min). (8,15) * a cut-off value of the ARR of 46 (plasma aldosterone in pmol/l in Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and renin in mU/l) (16)

Time frame: 3 months

Secondary Outcomes

Clinical success at 3 months

Clinical success, defined according to PASO outcome definitions at 3 months of follow-up, assessed by ambulotary blood pressure monitoring : * Complete clinical success: normal blood pressure without the aid of antihypertensive medication Partial clinical success: same blood pressure as before intervention†, with less antihypertensive medication‡ or a reduction in blood pressure with either the same amount or less antihypertensive medication * Absent clinical success: unchanged or increased blood pressure† with either the same amount or an increase in antihypertensive medication

Time frame: 3 months

Clinical success at 6 months

Clinical success, defined according to PASO outcome definitions at 6 months of follow-up, assessed by ambulotary blood pressure monitoring : * Complete clinical success: normal blood pressure without the aid of antihypertensive medication Partial clinical success: same blood pressure as before intervention†, with less antihypertensive medication‡ or a reduction in blood pressure with either the same amount or less antihypertensive medication * Absent clinical success: unchanged or increased blood pressure† with either the same amount or an increase in antihypertensive medication

Time frame: 6 months

Correction of hypokalaemia without supplementation or potassium sparing diuretic at 1 month of follow-up

Correction of hypokalaemia without supplementation or potassium sparing diuretic at 1 month of follow-up. Hypokalaemia is defined as serum potassium of \<3·6 mmol/L

Time frame: 1 month

Correction of hypokalaemia without supplementation or potassium sparing diuretic at 3 months of follow-up

Correction of hypokalaemia without supplementation or potassium sparing diuretic at 3 months of follow-up. Hypokalaemia is defined as serum potassium of \<3·6 mmol/L

Time frame: 3 months

Correction of hypokalaemia without supplementation or potassium sparing diuretic at 6 months of follow-up

Correction of hypokalaemia without supplementation or potassium sparing diuretic at 6 months of follow-up. Hypokalaemia is defined as serum potassium of \<3·6 mmol/L

Time frame: 6 months

Biochemical success at 3 months of follow-up

Biochemical success at 3 months of follow-up. Complete Biochemical success: correction of hypokalaemia (if present pre-intervention) and normalisation of the aldosterone-to-renin ratio Partial biochemical success: Correction of hypokalaemia (if present pre-intervention) and a raised aldosterone-to-renin ratio with one or both of the following (compared with pre-intervention): ≥50% decrease in baseline plasma aldosterone concentration; or abnormal but improved post-intervention confirmatory test result Absent biochemical success: Persistent hypokalaemia (if present pre-intervention) or persistent raised aldosterone-to-renin ratio, or both

Time frame: 3 months

mean changes in Blood Pressure values assessed by ABPM at 3 months

The mean changes in 24-hour, daytime and nocturnal Systolic BP/diastolic BP values will be assessed by ABPM between pre-inclusion and 3 months

Time frame: 3 months

mean changes in Blood Pressure values assessed by ABPM at 6 months

The mean changes in 24-hour, daytime and nocturnal Systolic BP/diastolic BP values will be assessed by ABPM between pre-inclusion and 6 months

Time frame: 6 months

normalisation of office BP at 6 months

The normalisation of office BP after 6-month of follow-up will be defined by Systolic BP/diastolic BP values \<140/90 mmHg without any treatment; BP will be measured with an oscillometric method: Dynamap, used in routine care, in a sitting position after 5 minutes' rest.

Time frame: 6 months

The use of antihypertensive agents at 6 months after RFA and after surgery

The use of antihypertensive agents at 6 months after RFA and after surgery. The number and defined daily dose (DDD, using the last index version, https://atcddd.fhi.no/atc\_ddd\_index/) of antihypertensive agents will be assessed

Time frame: 6 months

surface area destroyed by radiofrequency

In the RFA group, at 3 months of follow-up, the surface area destroyed and preservation of the adrenal gland around will be assessed by adrenal CT scan: Patients will undergo adrenal scan without and with injection of contrast product after verification of renal function.

Time frame: 3 months

Number of Adverse events

Adverse events will be collected and serious adverse events reported in the 2 groups at each visit until the end of the study

Time frame: 6 months

length of stay

Number of days of hospitalisation

Time frame: 6 months

Health economic criterion

Direct medical, non-medical costs and costs related to absence from the workplace

Time frame: 6 months

Radiofrequency Ablation Versus Adrenalectomy for Adenoma in Patients With Primary Aldosteronism and Hypertension

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts