HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients Undergoing Major Abdominal Surgery

Blood Pressure Clinical Trial

— HISTAP  

Official title:

HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients: The HISTAP Randomized Clinical Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05637606
• Other study ID #: HISTAP TRIAL
• Status: Recruiting
• Phase: N/A
• Start date: March 6, 2023
• Est. completion date: January 31, 2025

Study information

• Verified date: June 2024
• Source: Humanitas Clinical and Research Center
• Contact: Antonio Messina
• Phone: +390282241
• Email: antonio.messina[@]humanitas.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a multicenter randomized controlled trial comparing two strategies of mean arterial blood pressure management (MAP ≥ 80mmHg vs MAP ≥ 65 mmHg) in high-risk surgical patients undergoing elective laparotomic/laparoscopic surgery.

Description:

Intraoperative hypotension has been associated with major postoperative complications after non-cardiac surgery. However, is is still unclear the optimal intraoperative mean arterial pressure (MAP) target in the subgroup of those patient with an history of hypertension at home, and at risk of developing postoperative complications.

The objective of this study is to assess the effects of an intraoperative blood pressure management strategy aiming at keeping the MAP ≥ 80mmHg), as compared to the conventional practice (to maintain intraoperative MAP ≥ 65mmHg), on a composite outcome considering the death rate and the incidence of major events in patient scheduled for elective laparotomic/laparoscopic surgery.

The primary outcome is a composite of 30-days from operation mortality rate and at least one major organ dysfunction including the renal, respiratory, cardiovascular and neurologic systems or new onset of sepsis and septic shock occurring by day 7 after surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 636
• Est. completion date: January 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria (all the following)

1. Adult patients = 60 years

2. History of chronic hypertension requiring home therapy.

3. Scheduled for major elective abdominal surgery (laparoscopic, robotic or laparotomic)

4. Expected surgical duration of at least 3 hours.

5. Needing invasive arterial and hemodynamic monitoring as decided by the attending anesthetist, according to the rules of good clinical practice of each involved center.

AND

At increased risk of postoperative complications (at least one of the following):

1. American Society of Anesthesiologists (ASA) class 3 or 4

2. Known or documented history of coronary artery disease (angina, myocardial infarction or acute coronary syndrome).

3. Known or documented history of peripheral vascular disease.

4. Known or documented history of heart failure requiring treatment.

5. Ejection fraction less than 30% (echocardiography)

6. Signs of diastolic moderate to severe dysfunction or chronic hypertensive cardiomyopathy (echocardiography)

7. Moderate or severe valvular heart disease (echocardiography)

8. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Radiographically confirmed or according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

9. Diabetes currently treated with an oral hypoglycemic agent and/or insulin

10. Morbid obesity (BMI =35 kg/m2)

11. Preoperative serum albumin <30 g/l

12. Anaerobic threshold (if done) <14 ml/kg/min

13. Exercise tolerance equivalent to six metabolic equivalents (METs) or less as defined by American College of Cardiology/American Heart Association guidelines

Exclusion criteria

1. Refusal of consent

2. Chronic kidney disease with glomerular filtration rate <30 ml/min/1.73 m2 or requiring renal-replacement therapy for end-stage renal disease

3. Acute cardiovascular event, including acute or decompensated heart failure and acute coronary syndrome (within prior 30 days).

4. Urgent or time-critical surgery

5. Aortic or Renal vascular surgery (including nephrectomy)

6. Liver Surgery

7. Neurosurgery

8. Surgery for palliative treatment only or ASA physical status 5

9. Pregnancy

Related Conditions & MeSH terms

• Blood Pressure
• Complication,Postoperative
• Hypotension
• Intraoperative Hypotension
• Postoperative Complications

Intervention

Drug:
• Ephedrine
In both the group, the target MAP can be maintained by means of bolus of ephedrine (2.5 mg). The maximal dose for the ephedrine allowed is 25 mg (10 boluses of 2.5 mg), after this threshold a continuous infusion of norepinephrine will be started
• Norepinephrine
In both the group, the target MAP can be maintained by means of bolus of ephedrine (2.5 mg) or Etilefrine (1 mg). The continuous infusion of norepinephrine, as decided by the attending anesthetist, may be started at any point of the intraoperative period. The starting dose of norepinephrine is the lowest needed to reach the predefined MAP target.
• Etilefrine Hydrochloride bolus
The maximal dose for the etilefrine allowed is 10 mg (10 boluses of 1 mg), after this threshold a continuous infusion of norepinephrine will be started

Diagnostic Test:
• Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
PPV, SVV and mini_FC will guide fluid bolus administration during an episode of intraoperative hypotension, following two predefined algorithms for laparotomic/non laparotomic surgery

Locations

Country	Name	City	State
Italy	Fondazione Istituto San Raffaele G. Giglio	Cefalù	Sicilia
Italy	Department of Anesthesia, Critical Care and Pain Medicine, SS. Annunziata Hospital	Chieti	Abruzzo
Italy	Careggi University Hospital	Firenze	Toscana
Italy	Ospedali Riuniti Foggia- Università di Foggia	Foggia	Puglia
Italy	Division of Anesthesia and Intensive Care, University of Messina, Policlinico "G. Martino"	Messina	Sicilia
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan
Italy	Istituto Nazionale dei Tumori	Milano
Italy	Department of Anesthesia and Intensive Care, University Hospital of Modena	Modena	Emilia Romagna
Italy	Ospedale Antonio Cardarelli	Napoli
Italy	Department of Surgical Oncological and Oral Science, University of Palermo	Palermo	Sicilia
Italy	Azienda sanitaria Friuli Occidentale (AsFO]	Pordenone
Italy	Ospedale S. Anna di Castelnovo ne' Monti	Reggio Emilia
Italy	Policlinico A. Gemelli	Roma	Lazio
Italy	Humanitas Research Hospital	Rozzano	Milano
Italy	Ospedale Molinette	Torino
Italy	Unit of Anesthesiology and Intensive Care B, Department of Surgery, Dentistry, Gynecology and Pediatrics, AOUI-University Hospital Integrated Trust of Verona	Verona	Veneto

Sponsors (2)

Lead Sponsor	Collaborator
Humanitas Clinical and Research Center	Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva

Country where clinical trial is conducted

Italy, 

References & Publications (2)

Messina A, Robba C, Calabro L, Zambelli D, Iannuzzi F, Molinari E, Scarano S, Battaglini D, Baggiani M, De Mattei G, Saderi L, Sotgiu G, Pelosi P, Cecconi M. Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery. Crit Care. 2021 Feb 1;25(1):43. doi: 10.1186/s13054-021-03464-1. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CARDIOVASCULAR complications	Acute heart failure; Myocardial injury after non-cardiac surgery; Myocardial infarction; Bradycardia; Symptomatic proximal deep venous thrombosis; Peripheral arterial and venous thrombosis	day 7 after operation
Other	NEUROLOGICAL complications	Stroke; Subarachnoid hemorrhage; Cerebral venous thrombosis; Seizure; Acute delirium	day 7 after operation
Other	RESPIRATORY	Acute respiratory distress; Hypoxemia with or without acute respiratory distress; Need for invasive, non-invasive ventilation or high-flow nasal cannula for acute respiratory distress.; Acute respiratory distress syndrome.; Pulmonary edema; Pulmonary embolism	day 7 after operation
Other	RENAL	• Acute Kidney Injury (AKI) and AKI stages defined according to the AKIN classification/staging system of acute kidney injury	day 7 after operation
Other	SEPSIS and Septic shock	Based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria, sepsis required a quick Sequential Organ Failure Assessment (qSOFA) Score = 2 points due to infection, septic shock defined as indicated by the Surviving Sepsis Campaign Guidelines	day 7 after operation
Primary	Composite endpoint of postoperative mortality and at least one major organ dysfunction (see description in the secondary outcomes).	Composite postoperative outcome	up to 30 days after operation
Secondary	Hospital stay (days)	Hospital stay (days)	up to 30 days after operation
Secondary	ICU stay (days)	Intensive Care Unit stay (days)	up to 30 days after operation
Secondary	ICU readmission	Intensive Care Unit readmissions	up to 30 days after operation
Secondary	Sequential Organ Failure Assessment (SOFA) scores on postoperative	Postoperative organ failure - SOFA scores ranges from 0 (<2% of mortality) to 24 (>90% of mortality)	up to 7 days after operation
Secondary	Overall intraoperative fluid balance	Intraoperative infusions (crystalloids, colloids, blood products) / Intraoperative loss balance (urine output)	day 1 after the operation
Secondary	Mortality	Mortality	up to 30 days after operation
Secondary	Vasopressors use	Dose and timing of vasoactive drug infusion intraoperatively	day 1 after the operation
Secondary	Need for reoperation	Need of a new surgical treatment	day 30 after operation