| CTRI Number |
CTRI/2021/01/030199 [Registered on: 04/01/2021] Trial Registered Prospectively |
| Last Modified On: |
12/04/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Surgical/Anesthesia |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Continuation or stopping antihypertensives in patients undergoing non-cardiac surgery |
Scientific Title of Study
Modification(s)
|
The effect of continuation versus withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers on mortality and major adverse cardiovascular events in hypertensive patients undergoing elective non-cardiac surgery: An open-label randomised controlled trial |
| Trial Acronym |
ACE Trial |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Satyajeet Misra |
| Designation |
Additional Professor, Anesthesiology and Critical Care |
| Affiliation |
All India Institute of Medical Sciences (AIIMS), Bhubaneswar |
| Address |
Room no.409, Academic Block
AIIMS Bhubaneswar
Khordha
ORISSA
751019
India |
| Phone |
|
| Fax |
|
| Email |
misrasatyajeet@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Satyajeet Misra |
| Designation |
Additional Professor, Anesthesiology and Critical Care |
| Affiliation |
All India Institute of Medical Sciences (AIIMS), Bhubaneswar |
| Address |
Room no.409, Academic Block
AIIMS Bhubaneswar
Khordha
ORISSA
751019
India |
| Phone |
|
| Fax |
|
| Email |
misrasatyajeet@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Satyajeet Misra |
| Designation |
Additional Professor, Anesthesiology and Critical Care |
| Affiliation |
All India Institute of Medical Sciences (AIIMS), Bhubaneswar |
| Address |
Room no.409, Academic Block
AIIMS Bhubaneswar
Khordha
ORISSA
751019
India |
| Phone |
|
| Fax |
|
| Email |
misrasatyajeet@gmail.com |
|
|
Source of Monetary or Material Support
|
| Indian Council of Medical Research (ICMR), V. Ramalingaswami Bhawan, Ansari Nagar, New Delhi 110029 |
|
|
Primary Sponsor
|
| Name |
Dr Satyajeet Misra |
| Address |
Room no.409, Academic Block, AIIMS Bhubaneswar |
| Type of Sponsor |
Other [Self] |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Dr Raj Sahajanandan |
CMC Vellore |
| Dr Satyen Parida |
JIPMER Puducherry |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Satyajeet Misra |
AIIMS Bhubaneswar |
Room No 409
Academic Block, AIIMS Bhubaneswar
Bhubaneswar 751019
Khordha
ORISSA |
9438884048
misrasatyajeet@gmail.com |
| Dr Raj Sahajanandan |
CMC Vellore |
Department of Anesthesiology
CMC Vellore
Vellore
TAMIL NADU |
8489622336
rajsahajanandan@gmail.com |
| Dr Satyen Parida |
JIPMER Puducherry |
1st Floor, Superspeciality Block
JIPMER Puducherry
Pondicherry
PONDICHERRY |
9940973502
jipmersatyen@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee |
Approved |
| Institutional Review Board |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: O||Medical and Surgical, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Continuation of antihypertensive medications (ACE inhibitors/ARB) on the day of surgery |
The antihypertensive medications (ACE inhibitors/Angiotensin II receptor blockers) will be continued on the day of surgery in this group. Any other anti hypertensives that the patient is on will also be continued on the day of surgery. The dose of these drugs will be as prescribed by the cardiologist preoperatively. The frequency will be one dose of the drugs on the morning of surgery. |
| Intervention |
Stopping of antihypertensive medications (ACE inhibitors/ARB) before surgery. |
The antihypertensive medications (ACE inhibitors/ Angiotensin II receptor blockers) will be with held before surgery in this group. Any other antihypertensives that patient is on will be continued like beta blockers or calcium channel antagonists. Dose will be the same dose prescribed by the cardiologist preoperatively. Frequency will be on the morning of surgery. |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
All hypertensive adult patients, 18-70 years, on chronic ACEI/ARB therapy (defined as treatment of more than 3 months or at least 14 days) and undergoing elective major non-cardiac surgery (defined as surgery lasting more than 2 hours and/or with an expected postoperative hospital stay of at least 3 days) will be included in this trial |
|
| ExclusionCriteria |
| Details |
Patients undergoing emergency surgeries within 48 hours, those with preoperative hyperkalemia (serum potassium > 5.5 mmol/L), patients with severe chronic renal insufficiency or those requiring renal replacement therapy, patients in shock (defined as need for vasoactive drugs to maintain blood pressures before surgery), patients taking ACEI/ARBs for LV dysfunction, and patients with uncontrolled hypertension will be excluded. |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, variable |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
Blinding/Masking
Modification(s)
|
Open Label |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
Composite incidence of 30-day all-cause mortality, major adverse cardiovascular
events, and non-cardiovascular events (postoperative acute kidney injury, sepsis, respiratory failure requiring re-intubation, and unplanned ICU admissions due to any cause).
|
30 days after surgery. |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Episodes of hypotension |
Until 24 hours after surgery |
| Myocardial injury |
12/24 hours after surgery |
| Duration of primary hospital stay |
Till discharge from primary hospital |
| Hospital free days |
30 days of surgery |
| Duration of ICU stay |
Total duration of ICU stay |
| Intraoperative angioneurotic edema |
Intraoperative |
| Cancellation of cases due to rebound hypertension |
Preoperative |
| Postoperative hyperkalaemia requiring intervention |
Till discharge from ICU and/or hospital |
|
|
Target Sample Size
|
Total Sample Size="2000"
Sample Size from India="2000"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
04/01/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
Nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
The incidence of hypertension is increasing in the population and hypertensive patients routinely present for surgery and anesthesia. Angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB)s are commonly prescribed as first line antihypertensive agents to patients suffering from hypertension. These drugs are considered cardio protective and improve long term outcomes. However, patients who continue their ACEI/ARBs during surgery may have significant hypotension due to the effects of anesthesia and such hypotension is often difficult to treat. In addition, hypotension may worsen the postoperative outcomes and patients may have stroke, sepsis or acute kidney injury. However, withholding these drugs before surgery to minimise the incidence of hypotension and angioneurotic edema is also potentially risky as the continued benefits of cardio protection may be lost and patients may have major adverse cardiovascular events. Until date, there is no clear cut consensus on whether ACEI/ ARBs should be continued or withheld before surgery. Even multiple guidelines have differing recommendations with regards to continuation or withholding of ACEI/ARBs before surgery. Thus, this multi-centric open-label randomised controlled trial will look to address the issue by recruiting approximately 2100 patients, half of whom will be randomised to have their ACEI/ARBs withheld before surgery and the other half randomised to continue their medications on the day of surgery. The primary outcome that this trial will seek to address is the 30-day all cause mortality, incidence of major adverse cardiovascular and non-cardiovascular events in an effort to generate the evidence for best practices in this cohort of patients and address definitively the clinical conundrum that has vexed clinicians for more than two decades now. |