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CompletedNCT01669434Updated Sep 25, 2023Results posted

Chronic Angiotensin Converting Enzyme Inhibitors in Intermediate Risk Surgery

A Phase 4 interventional study of ACEI continuation and ACEI omission in Hypotension on Induction, sponsored by University of Nebraska. Completed at 1 site in United States. Open to participants aged 19 Years to 90 Years. Per ClinicalTrials.gov, last updated 2023-09-25.

Sponsored by University of Nebraska · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
291
Allocation
Randomized
Ages
19 Years to 90 Years
Sex
All
01

Study summary

Primary research hypothesis: Patients who continue their chronic ACEI therapy up to and including the morning of a non-cardiac, non-vascular surgery will experience more intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.

Secondary research hypothesis #1: Patients who continue their chronic ACEI up to and including the morning of a non-cardiac, non-vascular surgery will experience better postoperative control of hypertension than those who transiently hold their chronic ACEI preoperatively.

Secondary research hypothesis #2: Patients who continue their chronic ACEI up to and including the morning of a non-cardiac, non-vascular surgery will experience less acute renal failure than those who transiently hold their chronic ACEI preoperatively.

Secondary research hypothesis #3: In the subgroup of patients with a preoperative systolic blood pressure less than 110 mmHg, those who continue their chronic ACEI therapy up to and including the morning of a non-cardiac, non-vascular surgery will experience more intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.

Secondary research hypothesis #4: In the subgroup of patients above the age of 64, those who continue their chronic ACEI therapy up to and including the morning of a non-cardiac, non-vascular surgery will experience more intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.

Read the detailed description

The purpose of this study is to determine if transient discontinuation of angiotensin converting enzyme inhibitors (ACEIs) is necessary prior to non-cardiac, non-vascular surgery. ACEIs have been associated with intraoperative hypotension during vascular and cardiac surgeries. Patients presenting to the University of Nebraska Medical Center Pre-Anesthesia Screening (PAS) Clinic who are on chronic ACEI therapy will be eligible for enrollment. Subjects will be randomized to either omit or continue their ACEI preoperatively. The outcome of interest is intraoperative hypotension defined as a systolic blood pressure less than 80 mmHg. Blood pressure will be followed not only throughout surgery, but also during recovery and the remainder of hospitalization. Renal function will be assessed with creatinine measurements in the PAS clinic and on the first postoperative day. No follow-up is planned beyond discharge from the hospital.

02

Conditions studied

  • Hypotension on Induction

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Keywords

  • Perioperative Period
03

In context

Hypotension

1,004 studies on the registry are indexed under Hypotension; 172 are open to participants now.

This study's enrollment of 291 is above the median of 80 across 676 interventional studies indexed under Hypotension.

Browse Hypotension studies →

Lead sponsor

University of Nebraska is the lead sponsor of 474 studies on the registry; 66 are open to participants now.

Of its 75 completed or terminated interventional studies of FDA-regulated products, 46 (61%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
19 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Referred to the University of Nebraska Medical Center Pre-Anesthesia Screening Clinic for preoperative evaluation.
  • Above referral must be in anticipation of a non-cardiac, non-vascular surgery.
  • Must have been on ACE-Inhibitor therapy for at least six weeks.

Exclusion criteria

Exclusion Criteria:

  • Hypotension (systolic blood pressure \< 90 or diastolic blood pressure \<60) at the time of preoperative evaluation
  • Uncontrolled Hypertension (systolic blood pressure > 150 or diastolic blood pressure > 95) at the time of preoperative evaluation
  • Surgery during which vasopressor use is anticipated (carotid endarterectomy, major abdominal operations, orthopedic oncology)
  • Surgery for pathology related to vasoactive substances (carcinoid, pheochromocytoma)
  • Left Ventricular ejection fraction less than 40%
  • Clinical evidence of decompensated heart failure at the time of preoperative evaluation
  • End-stage renal disease
  • Organ transplant surgeries
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Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
291 participants (actual)

Study arms

  • Experimental
    ACEI continuation

    Patients in this arm will be randomized to continue their chronic angiotensin converting enzyme inhibitor without interruption preoperatively

    Drug: ACEI continuation

  • Experimental
    ACEI omission

    Patients randomized to this arm will be told to omit their final preoperative chronic angiotensin converting enzyme inhibitor dose.

    Drug: ACEI omission

Interventions

  • DrugACEI continuation

    These chronic medications will be taken without interruption preoperatively.

    Also known as: quinapril, Accupril, perindopril, Aceon, ramipril, Altace, benazepril, Lotensin, captopril, Capoten, enalapril, Vasotec, fosinopril, Monopril, lisinopril, Prinivil, Zestril, trandolapril, Mavik, moexipril, Univasc

  • DrugACEI omission

    Although taken chronically by patients in this intervention, the final preoperative dose of these medications will be omitted, whether it was scheduled for the morning of surgery or the day prior.

    Also known as: quinapril, Accupril, perindopril, Aceon, ramipril, Altace, benazepril, Lotensin, captopril, Capoten, enalapril, Vasotec, fosinopril, Monopril, lisinopril, Prinivil, Zestril, trandolapril, Mavik, moexipril, Univasc

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What researchers measure

Primary outcomes

  1. Number of Participants With Interoperative Hypotension

    Number of Participants with Interoperative Hypotension (systolic blood pressure under 80 mmHg)

    Time frame: During anesthesia, an expected average of 3 hours.

Secondary outcomes

  1. Acute Renal Failure

    Creatinine increase of more than 0.3 mg/dl or more than 50% from preoperative level

    Time frame: Arrival in post-anesthesia care unit (PACU) to hospital discharge, an expected average of 4 days.

  2. Low Blood Pressure Subgroup

    Only patients with systolic blood pressure less than 110 at preoperative evaluation will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg.

    Time frame: During anesthesia, an expected average of 3 hours.

  3. Older Age Subgroup

    Only patients above the age of 64 will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg

    Time frame: During anesthesia, an expected average of 3 hours.

  4. Postoperative Hypertension

    Any systolic blood pressure greater than 180 mmHg.

    Time frame: Arrival in PACU to hospital discharge, an expected average of 4 days.

  5. Postoperative Hypotension

    Any systolic blood pressure less than 90 mmHg

    Time frame: Arrival in PACU to hospital discharge, an expected average of 4 days.

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Results

Posted Dec 11, 2017
Limitations and caveats
Management decisions were made by the treatment which was not blinded to allocation; Intraoperative hypotension is an intermediate measure but one that has known associations with adverse outcomes, including mortality.

Participant flow

Participant flow — Overall Study
MilestoneACEI OmissionACEI Continuation
Started146145
Completed137138
Not completed97

Outcome measures

PrimaryNumber of Participants With Interoperative Hypotension

Number of Participants with Interoperative Hypotension (systolic blood pressure under 80 mmHg)

Time frame:
During anesthesia, an expected average of 3 hours.
Reported as:
Count of participants · Participants
Number of Participants With Interoperative Hypotension
ParticipantsACEI OmissionACEI Continuation
Number of Participants With Interoperative Hypotension7695
Statistical analysis
  • ACEI Omission vs ACEI Continuation · Fisher Exact · p = 0.03 · Risk ratio (rr): 0.81 · 95% CI 0.67 to 0.97
SecondaryAcute Renal Failure

Creatinine increase of more than 0.3 mg/dl or more than 50% from preoperative level

Time frame:
Arrival in post-anesthesia care unit (PACU) to hospital discharge, an expected average of 4 days.
Reported as:
Count of participants · Participants
Acute Renal Failure
ParticipantsACEI OmissionACEI Continuation
Acute Renal Failure610
Statistical analysis
  • ACEI Omission vs ACEI Continuation · Fisher Exact · p = 0.44 · Risk ratio (rr): 0.60 · 95% CI 0.23 to 1.60
SecondaryLow Blood Pressure Subgroup

Only patients with systolic blood pressure less than 110 at preoperative evaluation will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg.

Time frame:
During anesthesia, an expected average of 3 hours.
Reported as:
Count of participants · Participants
Low Blood Pressure Subgroup
ParticipantsACEI OmissionACEI Continuation
Low Blood Pressure Subgroup42
Statistical analysis
  • ACEI Omission vs ACEI Continuation · Fisher Exact · p = 1.0 · Risk ratio (rr): 1.20 · 95% CI 0.48 to 2.99
SecondaryOlder Age Subgroup

Only patients above the age of 64 will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg

Time frame:
During anesthesia, an expected average of 3 hours.
Reported as:
Count of participants · Participants
Older Age Subgroup
ParticipantsACEI OmissionACEI Continuation
Older Age Subgroup4849
Statistical analysis
  • ACEI Omission vs ACEI Continuation · Fisher Exact · p = 1.0 · Risk ratio (rr): 1.01 · 95% CI 0.81 to 1.26
SecondaryPostoperative Hypertension

Any systolic blood pressure greater than 180 mmHg.

Time frame:
Arrival in PACU to hospital discharge, an expected average of 4 days.
Reported as:
Count of participants · Participants
Postoperative Hypertension
ParticipantsACEI OmissionACEI Continuation
Postoperative Hypertension3317
Statistical analysis
  • ACEI Omission vs ACEI Continuation · Fisher Exact · p = 0.01 · Risk ratio (rr): 1.95 · 95% CI 1.14 to 3.34
SecondaryPostoperative Hypotension

Any systolic blood pressure less than 90 mmHg

Time frame:
Arrival in PACU to hospital discharge, an expected average of 4 days.
Reported as:
Count of participants · Participants
Postoperative Hypotension
ParticipantsACEI OmissionACEI Continuation
Postoperative Hypotension1531
Statistical analysis
  • ACEI Omission vs ACEI Continuation · Fisher Exact · p = 0.02 · Risk ratio (rr): 0.49 · 95% CI 0.28 to 0.86

Adverse events

Collected over Hospitalization, expected duration 4 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ACEI Omission0/137 (0%)4/137 (2.9%)0/137 (0%)
ACEI Continuation0/138 (0%)1/138 (0.7%)0/138 (0%)
Most frequent serious events
Most frequent serious events
EventACEI OmissionACEI Continuation
MACECardiac disorders4/1371/138

Baseline characteristics

Age, Continuous
Age, Continuous(years)ACEI OmissionACEI ContinuationTotal
Mean64 (26 to 91)63.7 (31 to 86)63.9 (26 to 91)
Sex: Female, Male
Sex: Female, Male(Participants)ACEI OmissionACEI ContinuationTotal
Female7270142
Male6568133
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)ACEI OmissionACEI ContinuationTotal
Caucasian115125240
Black151126
Hispanic202
Am Indian/Alaska213
Other/Unknown314
Region of Enrollment
Region of Enrollment(participants)ACEI OmissionACEI ContinuationTotal
United States137138275
smoking status
smoking status(Participants)ACEI OmissionACEI ContinuationTotal
Never6354117
Former6059119
Current142539
American Society of Anesthesiologists classification
American Society of Anesthesiologists classification(units on a scale)ACEI OmissionACEI ContinuationTotal
Mean2.8 (1 to 4)2.8 (2 to 4)2.8 (1 to 4)
preoperative NSAID use
preoperative NSAID use(Participants)ACEI OmissionACEI ContinuationTotal
Count of participants5371124
preoperative systolic BP
preoperative systolic BP(mmHg)ACEI OmissionACEI ContinuationTotal
Mean136.6 (99 to 187)136.3 (102 to 184)136.5 (99 to 187)

3 further baseline measures are reported on the registry.

08

Study locations

1 site
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
09

References and documents

Publications

  • McConachie I, Healy TE. ACE inhibitors and anaesthesia. Postgrad Med J. 1989 May;65(763):273-4. doi: 10.1136/pgmj.65.763.273. No abstract available. PubMed 2692007 ↗
  • Coriat P, Richer C, Douraki T, Gomez C, Hendricks K, Giudicelli JF, Viars P. Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction. Anesthesiology. 1994 Aug;81(2):299-307. doi: 10.1097/00000542-199408000-00006. PubMed 8053578 ↗
  • Comfere T, Sprung J, Kumar MM, Draper M, Wilson DP, Williams BA, Danielson DR, Liedl L, Warner DO. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005 Mar;100(3):636-644. doi: 10.1213/01.ANE.0000146521.68059.A1. PubMed 15728043 ↗
  • Pigott DW, Nagle C, Allman K, Westaby S, Evans RD. Effect of omitting regular ACE inhibitor medication before cardiac surgery on haemodynamic variables and vasoactive drug requirements. Br J Anaesth. 1999 Nov;83(5):715-20. doi: 10.1093/bja/83.5.715. PubMed 10690132 ↗
  • Steiner CA, Karaca Z, Moore BJ, Imshaug MC, Pickens G. Surgeries in Hospital-Based Ambulatory Surgery and Hospital Inpatient Settings, 2014. 2017 May [updated 2020 Jul 20]. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #223. Available from http://www.ncbi.nlm.nih.gov/books/NBK442035/ PubMed 28722845 ↗
  • Rate of all-listed procedures for discharges from short-stay hospitals, by procedure category and age: United States, 2010. 2010.
  • Turan A, You J, Shiba A, Kurz A, Saager L, Sessler DI. Angiotensin converting enzyme inhibitors are not associated with respiratory complications or mortality after noncardiac surgery. Anesth Analg. 2012 Mar;114(3):552-60. doi: 10.1213/ANE.0b013e318241f6af. Epub 2012 Jan 17. PubMed 22253266 ↗
  • Mascha EJ, Yang D, Weiss S, Sessler DI. Intraoperative Mean Arterial Pressure Variability and 30-day Mortality in Patients Having Noncardiac Surgery. Anesthesiology. 2015 Jul;123(1):79-91. doi: 10.1097/ALN.0000000000000686. PubMed 25929547 ↗
  • Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26. PubMed 23835589 ↗
  • Bertrand M, Godet G, Meersschaert K, Brun L, Salcedo E, Coriat P. Should the angiotensin II antagonists be discontinued before surgery? Anesth Analg. 2001 Jan;92(1):26-30. doi: 10.1097/00000539-200101000-00006. PubMed 11133595 ↗
  • Roshanov PS, Rochwerg B, Patel A, Salehian O, Duceppe E, Belley-Cote EP, Guyatt GH, Sessler DI, Le Manach Y, Borges FK, Tandon V, Worster A, Thompson A, Koshy M, Devereaux B, Spencer FA, Sanders RD, Sloan EN, Morley EE, Paul J, Raymer KE, Punthakee Z, Devereaux PJ. Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort. Anesthesiology. 2017 Jan;126(1):16-27. doi: 10.1097/ALN.0000000000001404. PubMed 27775997 ↗
  • Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, Davila-Roman VG, Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky BF, Wijeysundera DN; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014 Dec 9;64(22):e77-137. doi: 10.1016/j.jacc.2014.07.944. Epub 2014 Aug 1. No abstract available. PubMed 25091544 ↗
  • Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, Hert SD, Ford I, Gonzalez-Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luscher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Sousa-Uva M, Voudris V, Funck-Brentano C; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014 Sep 14;35(35):2383-431. doi: 10.1093/eurheartj/ehu282. Epub 2014 Aug 1. No abstract available. PubMed 25086026 ↗
  • Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713. PubMed 17331245 ↗
  • Monk TG, Bronsert MR, Henderson WG, Mangione MP, Sum-Ping ST, Bentt DR, Nguyen JD, Richman JS, Meguid RA, Hammermeister KE. Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery. Anesthesiology. 2015 Aug;123(2):307-19. doi: 10.1097/ALN.0000000000000756. Erratum In: Anesthesiology. 2016 Mar;124(3):741-2. doi: 10.1097/01.anes.0000479922.33134.89. PubMed 26083768 ↗
  • Kheterpal S, Khodaparast O, Shanks A, O'Reilly M, Tremper KK. Chronic angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy combined with diuretic therapy is associated with increased episodes of hypotension in noncardiac surgery. J Cardiothorac Vasc Anesth. 2008 Apr;22(2):180-6. doi: 10.1053/j.jvca.2007.12.020. PubMed 18375317 ↗
  • Twersky RS, Goel V, Narayan P, Weedon J. The risk of hypertension after preoperative discontinuation of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists in ambulatory and same-day admission patients. Anesth Analg. 2014 May;118(5):938-44. doi: 10.1213/ANE.0000000000000076. PubMed 24681657 ↗
  • Tan TW, Eslami MH, Kalish JA, Eberhardt RT, Doros G, Goodney PP, Cronenwett JL, Farber A; Vascular Study Group of New England. The need for treatment of hemodynamic instability following carotid endarterectomy is associated with increased perioperative and 1-year morbidity and mortality. J Vasc Surg. 2014 Jan;59(1):16-24.e1-2. doi: 10.1016/j.jvs.2013.07.025. Epub 2013 Aug 30. PubMed 23994095 ↗
  • Lee SM, Takemoto S, Wallace AW. Association between Withholding Angiotensin Receptor Blockers in the Early Postoperative Period and 30-day Mortality: A Cohort Study of the Veterans Affairs Healthcare System. Anesthesiology. 2015 Aug;123(2):288-306. doi: 10.1097/ALN.0000000000000739. PubMed 26200181 ↗
  • Drenger B, Fontes ML, Miao Y, Mathew JP, Gozal Y, Aronson S, Dietzel C, Mangano DT; Investigators of the Ischemia Research and Education Foundation; Multicenter Study of Perioperative Ischemia Research Group. Patterns of use of perioperative angiotensin-converting enzyme inhibitors in coronary artery bypass graft surgery with cardiopulmonary bypass: effects on in-hospital morbidity and mortality. Circulation. 2012 Jul 17;126(3):261-9. doi: 10.1161/CIRCULATIONAHA.111.059527. Epub 2012 Jun 19. PubMed 22715473 ↗
  • Shiffermiller JF, Monson BJ, Vokoun CW, Beachy MW, Smith MP, Sullivan JN, Vasey AJ, Guda P, Lyden ER, Ellis SJ, Pang H, Thompson RE. Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI). J Hosp Med. 2018 Sep;13(10):661-667. doi: 10.12788/jhm.3036. Epub 2018 Jul 25. PubMed 30261084 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 25, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01669434
Lead sponsor
University of Nebraska
Responsible party
Sponsor
First posted
Aug 21, 2012
Start date
Jun 1, 2015
Primary completion
Nov 1, 2016
Completion
Dec 1, 2016
Results posted
Dec 11, 2017
Last update
Sep 25, 2023

Study contacts

Jason F Shiffermiller, MD, MPH
principal investigator · University of Nebraska

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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