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

NCT05637606 | Completed DMC

• 1 other identifier: HISTAP TRIAL
• Study Type: interventional
• Target: 636
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

Blood Pressure; Complication,Postoperative; Intraoperative Hypotension

Keywords

Blood pressure; Intraoperative Hypotension; Postoperative complications; Postoperative mortality

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Hospital stay (days)

  up to 30 days after operation

• ICU stay (days)

  up to 30 days after operation

• ICU readmission

  up to 30 days after operation

• Sequential Organ Failure Assessment (SOFA) scores on postoperative

  up to 7 days after operation

• Overall intraoperative fluid balance

  day 1 after the operation

Other Outcomes (5)

• CARDIOVASCULAR complications

  day 7 after operation

• NEUROLOGICAL complications

  day 7 after operation

• RESPIRATORY

  day 7 after operation

Study Arms (2)

MAP 80

EXPERIMENTAL

Intervention group: intraoperative mean blood pressure target \> 80 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 80 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.

Drug: Ephedrine; Drug: Norepinephrine; Drug: Etilefrine Hydrochloride bolus; Diagnostic Test: Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)

MAP 65

OTHER

Control group: intraoperative mean blood pressure target \> 65 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 65 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.

Drug: Ephedrine; Drug: Norepinephrine; Drug: Etilefrine Hydrochloride bolus; Diagnostic Test: Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)

Interventions

Ephedrine DRUG

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

Also known as: Ephedrine bolus

MAP 65; MAP 80

Norepinephrine DRUG

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.

Also known as: norepinephrine infusion

MAP 65; MAP 80

Etilefrine Hydrochloride bolus DRUG

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

MAP 65; MAP 80

Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC) DIAGNOSTIC_TEST

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

Also known as: Hemodynamic optimization

MAP 65; MAP 80

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 60 years
• History of chronic hypertension requiring home therapy.
• Scheduled for major elective abdominal surgery (laparoscopic, robotic or laparotomic)
• Expected surgical duration of at least 3 hours.
• 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):
• American Society of Anesthesiologists (ASA) class 3 or 4
• Known or documented history of coronary artery disease (angina, myocardial infarction or acute coronary syndrome).
• Known or documented history of peripheral vascular disease.
• Known or documented history of heart failure requiring treatment.
• Ejection fraction less than 30% (echocardiography)
• Signs of diastolic moderate to severe dysfunction or chronic hypertensive cardiomyopathy (echocardiography)
• Moderate or severe valvular heart disease (echocardiography)
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Radiographically confirmed or according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

You may not qualify if:

• Refusal of consent
• Chronic kidney disease with glomerular filtration rate \<30 ml/min/1.73 m2 or requiring renal-replacement therapy for end-stage renal disease
• Acute cardiovascular event, including acute or decompensated heart failure and acute coronary syndrome (within prior 30 days).
• Urgent or time-critical surgery
• Aortic or Renal vascular surgery (including nephrectomy)
• Liver Surgery
• Neurosurgery
• Surgery for palliative treatment only or ASA physical status 5
• Pregnancy

Sponsors & Collaborators

• Humanitas Clinical and Research Center: lead
• Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva: collaborator

Study Sites (18)

Ospedali Riuniti Foggia- Università di Foggia

Foggia, Apulia, Italy

Location

Department of Anesthesia and Intensive Care, University Hospital of Modena

Modena, Emilia-Romagna, Italy

Location

Policlinico A. Gemelli

Rome, Lazio, Italy

Location

Humanitas Research Hospital

Rozzano, MILANO, 20089, Italy

Location

Fondazione Istituto San Raffaele G. Giglio

Cefalù, Sicily, Italy

Location

Careggi University Hospital

Florence, Tuscany, 50134, Italy

Location

Unit of Anesthesiology and Intensive Care B, Department of Surgery, Dentistry, Gynecology and Pediatrics, AOUI-University Hospital Integrated Trust of Verona

Verona, Veneto, Italy

Location

Azienda Ospedaliero - Universitaria SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Istituto Nazionale dei Tumori

Milan, Italy

Location

Ospedale Antonio Cardarelli

Napoli, Italy

Location

Azienda sanitaria Friuli Occidentale (AsFO]

Pordenone, Italy

Location

Ospedale Santo Stefano

Prato, Italy

Location

Ospedale S. Anna di Castelnovo ne' Monti

Reggio Emilia, Italy

Location

Sant'Eugenio ASL Roma 2:

Roma, Italy

Location

Azienda Ospedaliero Universitaria di Sassari

Sassari, Italy

Location

Ospedale Molinette

Torino, Italy

Location

Ospedale Santa Chiara di Trento

Trento, Italy

Location

Related 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.

  PMID: 33522953 BACKGROUND

• 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.

  PMID: 23835589 BACKGROUND

MeSH Terms

Conditions

Postoperative Complications

Interventions

Ephedrine; Norepinephrine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Antonio Messina

  Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The trial intervention is not blinded for investigators, clinical staff, and patients, as blinding intraoperative MAP target is not feasible. The physicians of each center assessing all postoperative outcomes will be masked for the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study will be a multicentric, randomized, non-blinded clinical trial. Eligible patients will be assigned in a 1:1 ratio to either a to control or treatment group. Randomization list will be created by a computer with the use of a permuted block design and embedded in the Electronic Case Report Form. Randomization will be performed using a 'block of 6" and stratified according to predefined baseline characteristics: 1. Age ≥ 75 years 2. Preoperative systolic pressure 1. \< 140 mmHg 2. ≥ 140 mmHg

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 5, 2022
• Study Start: March 6, 2023
• Primary Completion: May 21, 2025
• Study Completion: May 21, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

IT (18)