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Cancer SurgeryPRIMENCT06744413

Prehabilitation to Improve Heart Rate Variability (PRIME)

A study testing Multimodal prehabilitation program in people with Cancer Surgery, run by Università Vita-Salute San Raffaele at 4 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Cancer patients require chronic management and care. For those individuals living with cancer, a comprehensive approach that acknowledges the interdisciplinary nature of their condition can help guide appropriate care strategies and support their overall well-being. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer Surgery
What is being tested?
Multimodal prehabilitation program
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
4 sitesItaly
Study dates
20 Dec 2024to Nov 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Scheduled to undergo elective major abdominal or thoracic cancer surgery;
  • Scheduled to undergo surgery at least three weeks after enrollment;
  • Age ≥ 18 years;
  • Provide written informed consent;
  • Willing and able to use smartphone application.

Who cannot join

  • Presenting with very poor functional capacity;
  • American Society of Anesthesiologists (ASA) physical status classes 5-6;
  • Disabling orthopedic, neuromuscular, and psychiatric diseases or other conditions that preclude participation in a prehabilitation program.

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Fabio Guarracino, Dr contact

+393281652528

f.guarracino@ao-pisa.toscana.it

Italy4 sites, 3 recruiting

  • Azienda Ospedaliero Universitaria Policlinico San Marco di Catania

    Catania, 95100

    Active, not recruiting

  • Università di Foggia

    Foggia, 71100

    Gilda Cinnella, Medical Doctor, +393204394598, gilda.cinnella@unifg.it

    Recruiting

  • IRCCS Ospedale San Raffaele

    Milan, 20132

    Giovanni G Landoni, Full Professor, +393472520801, landoni.giovanni@hsr.it

    Recruiting

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56126

    Fabio Guarracino, Medical Doctor, +393281652528, f.guarracino@ao-pisa.toscana.it

    Recruiting

Other trials in Italy

About this study

Official title: Prehabilitation to Improve Heart Rate Variability In Surgical Cancer Patients: a randoMized controllEd Trial

Cancer patients require chronic management and care. For those individuals living with cancer, a comprehensive approach that acknowledges the interdisciplinary nature of their condition can help guide appropriate care strategies and support their overall well-being. Approximately 45% of patients diagnosed with cancer undergo surgery to remove their tumor. Despite the advancements in surgical techniques, anesthesia, and perioperative care, major cancer surgeries still pose a significant challenge leading to a considerable decline in physiological and functional capacity. Traditionally, efforts focused on postoperative rehabilitation to enhance recovery. Recently, prehabilitation, a form of rehabilitation which aims to improve functional capacity before surgery, has gained attention for its potential benefits in improving surgical outcomes. However, prehabilitation lacks objective assessment measures to evaluate its effectiveness. Developing validated outcome measures is essential to enhance the impact of prehabilitation on surgical outcomes and long-term care for cancer patients. Heart rate variability (HRV) is a physiological parameter that measures the variation in time intervals between consecutive heartbeats, reflecting the autonomic nervous system activity which might serve as a valuable solution for objective outcome measures in evaluating the effectiveness of prehabilitation for cancer patients, providing an objective tool to assess and monitor physiological response to stress, recovery capacity, and autonomic nervous system activity. A multicenter randomized controlled trial will be conducted to assess the impact of a multimodal prehabilitation program on HRV. Patients aged 18 or older, scheduled for elective major cancer surgery will be randomized to receive either prehabilitation or standard care. The prehabilitation arm will receive a program involving home-based physical, nutritional, and psychological interventions for at least four weeks. Participants allocated to the control group will receive usual care. Patients will be followed throughout the study using an innovative mobile application, allowing for real-time monitoring and data collection during the prehabilitation program. The study has two primary outcomes: A) to assess the impact of prehabilitation on increasing preoperative HRV in chronic cancer patients undergoing surgery; B) to assess the effect of prehabilitation on length of hospital stay.

Read the detailed description

Cancer patients require long-term management and ongoing care due to the chronic nature of their condition. Major cancer surgeries pose significant challenges, resulting in a decline in physiological and functional capacity. Traditionally, postoperative rehabilitation has been the most suitable intervention to improve functional recovery. Prehabilitation, which aims to enhance patients' functional capacity before surgery and to improve patients' ability to cope with physiological stress, is considered the best form of rehabilitation. Through multimodal strategies like exercise, nutrition and psychological support, prehabilitation can improve surgical outcomes for cancer patients. However, prehabilitation lacks objective assessment measures. Heart rate variability (HRV), a physiological parameter measuring variation in heartbeats, reflects autonomic nervous system activity and an increase in HRV is associated with fitness and recovery capacity in sports medicine. Psychological factors, nutritional status and physical exercise influence HRV. Hence, HRV could be used to objectively assess prehabilitation interventions. In addition, HRV is widely used in risk assessment in cardiology, and a reduction in HRV is recognized to be associated with complications and mortality. Despite its evident potential in risk assessment, HRV has never been utilized in preoperative assessments.

This is an international, multicenter, parallel-group, randomized study in chronic cancer patients undergoing surgery. Adult men and women patients who are eligible according to the inclusion/exclusion criteria will be randomized to study the effect of prehabilitation versus standard care on heart rate variability (HRV).

A total of 600 patients will be recruited by systematic screening of patients scheduled for elective surgical procedures. All patients undergoing major cancer surgery will be screened for eligibility and those who meet the inclusion/exclusion criteria will be approached for consent. Research personnel will use a web-based randomization system to assign patients (1:1 ratio) to either the prehabilitation or control arm. Study personnel will also collect data on recruitment rates, with reasons for non-enrollment.

Eligible patients will be randomly assigned to one of two treatments:

  1. Multimodal prehabilitation program for four weeks starting as soon as possible before surgery;
  2. Standard care.

The multimodal prehabilitation program will be individualized by carefully integrating and adapting various components to meet individual needs. The program will last four weeks (plus maintenance in case of delayed surgery), and will incorporate exercise training, nutritional therapy, and anxiety reduction techniques. After enrollment, patients will receive initial contact from trained personnel through telemedicine. To ensure personalized care, a comprehensive assessment will be conducted to identify specific physical, nutritional, or psychological challenges. Based on this assessment, a customized intervention plan will be prescribed to achieve tailored exercise training, optimized nutrition, and effective distress-coping strategies. Patients will be requested to download a dedicated smartphone application, which will comprehensively monitor and track their progress towards achieving their prehabilitation goals. After completing the four-week program, patients will continue a maintenance program until surgery.

The first HRV measurement will be performed for 5 minutes in an isolated room, after signing the written consent and before randomization, on the day of screening which occurs several weeks before surgery. The second HRV measurement will be performed the day before surgery. Both HRV time-domain measurements and HRV frequency-domain measurements will be evaluated.

Conditions
Cancer Surgery
Being tested
Multimodal prehabilitation program
Keywords
Cancer surgery, Prehabilitation, Multimodal prehabilitation program, Standard care treatment, Hospital stay, Functional walking, Nutrition, Diet, Exercise, Relaxation, Functional recovery, Anesthesiology
Medical subject headings
Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Multimodal prehabilitation programBehavioural

    A tailored intervention will be prescribed if specific physical, nutritional or psychological impairments will be identified during the assessment phase. Based on the data obtained during the multimodal assessment, different domains and levels of care will be prescribed, focusing on exercise training, and/or nutrition optimization, and/or distress-coping techniques. Different combinations of these three domains will be utilized to maximize their synergistic anabolic effect.

    The duration of the program will be set at 4 weeks.

Study groups in NCT06744413
Study groupRoleWhat they receive
PrehabilitationExperimentalPrehabilitation arm groups will receive preoperative intervention which includes exercise training, nutritional therapy and anxiety reducing techniques, aimed at preventing or attenuating surgery-driven functional decline.
Receives: Behavioral: Multimodal prehabilitation program
Control groupNo interventionStandard care treatment: application of ERAS pathways (Enhanced Recovery After Surgery)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assess the impact of prehabilitation on heart rate variability

    This primary outcome measure will be the change in the standard deviation of normal-to-normal intervals (SDNN) from baseline to the day before surgery.

    Measured: Preoperative

  2. Days at home within first 30 days after surgery

    The mean number of days at home in the first 30 days after surgery will be compared between groups

    Measured: 30-days after surgery

Secondary outcomes (5)

  1. Quality of life at 30 days

    Assess quality of life in the first 30 days at home after surgery using the EuroQol-5 Dimension (EQ-5D-5L) questionnaire, a validated tool for evaluating health-related quality of life. The outcome will be reported as the mean EQ-5D-5L index score and the mean EQ-VAS score measured at 30 days postoperatively.

    Measured: 30-days after surgery

  2. 30-days postoperative complication

    Assess the occurrence of postoperative complications in the first 30 days after surgery

    Measured: 30-days after surgery

  3. Correlation between preoperative standard deviation of all normal to normal R-R intervals (SDNN) and quality of life at 30 days postoperatively

    Investigate the association between preoperative heart rate variability (HRV) and life at 30 days postoperatively

    Measured: 30-days after surgery

  4. Correlation between preoperative SDNN and DAH-30

    Investigate the association between preoperative heart rate variability (HRV) and the days alive and at home within 30 days after surgery (DAH-30)

    Measured: 30-days after surgery

  5. Correlation between preoperative SDNN and postoperative complication

    Investigate the association between preoperative heart rate variability (HRV) and postoperative complication

    Measured: 30-days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2024
  2. Study start20 Dec 2024
  3. Primary completionAug 2026 (estimated)
  4. Study completionNov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06744413
Sponsor's protocol ID
PNRR-MCNT2-2023-12377934
Acronym
PRIME
Status last verified
Aug 2025
First submitted
12 Dec 2024
Last updated
6 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. Am J Epidemiol. 1989 Apr;129(4):687-702.

    PubMed 2646917

  • Zhou X, Ma Z, Zhang L, Zhou S, Wang J, Wang B, Fu W. Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis. J Psychosom Res. 2016 Oct;89:20-5. doi: 10.1016/j.jpsychores.2016.08.004. Epub 2016 Aug 8.

    PubMed 27663106

  • Thompson PD, Arena R, Riebe D, Pescatello LS; American College of Sports Medicine. ACSM's new preparticipation health screening recommendations from ACSM's guidelines for exercise testing and prescription, ninth edition. Curr Sports Med Rep. 2013 Jul-Aug;12(4):215-7. doi: 10.1249/JSR.0b013e31829a68cf. No abstract available.

    PubMed 23851406

  • Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

    PubMed 8598068

  • Tarvainen MP, Niskanen JP, Lipponen JA, Ranta-Aho PO, Karjalainen PA. Kubios HRV--heart rate variability analysis software. Comput Methods Programs Biomed. 2014;113(1):210-20. doi: 10.1016/j.cmpb.2013.07.024. Epub 2013 Aug 6.

    PubMed 24054542

  • Scheede-Bergdahl C, Minnella EM, Carli F. Multi-modal prehabilitation: addressing the why, when, what, how, who and where next? Anaesthesia. 2019 Jan;74 Suppl 1:20-26. doi: 10.1111/anae.14505.

    PubMed 30604416

  • Orange ST, Northgraves MJ, Marshall P, Madden LA, Vince RV. Exercise prehabilitation in elective intra-cavity surgery: A role within the ERAS pathway? A narrative review. Int J Surg. 2018 Aug;56:328-333. doi: 10.1016/j.ijsu.2018.04.054. Epub 2018 May 3.

    PubMed 29730070

  • Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, Baig W, Flapan AD, Cowley A, Prescott RJ, Neilson JM, Fox KA. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation. 1998 Oct 13;98(15):1510-6. doi: 10.1161/01.cir.98.15.1510.

    PubMed 9769304

  • Myles PS, Shulman MA, Heritier S, Wallace S, McIlroy DR, McCluskey S, Sillar I, Forbes A. Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia. BMJ Open. 2017 Aug 18;7(8):e015828. doi: 10.1136/bmjopen-2017-015828.

    PubMed 28821518

  • Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D, Christophi C, Leslie K, McGuinness S, Parke R, Serpell J, Chan MTV, Painter T, McCluskey S, Minto G, Wallace S; Australian and New Zealand College of Anaesthetists Clinical Trials Network and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery. N Engl J Med. 2018 Jun 14;378(24):2263-2274. doi: 10.1056/NEJMoa1801601. Epub 2018 May 9.

    PubMed 29742967

  • Mostarda C, Castro-Filha J, Reis AD, Sevilio M Jr, Dias CJ, Silva-Filho AC, Garcia JBS, do Desterro Nascimento M, Coelho-Junior HJ, Rodrigues B. Short-term combined exercise training improves cardiorespiratory fitness and autonomic modulation in cancer patients receiving adjuvant therapy. J Exerc Rehabil. 2017 Oct 30;13(5):599-607. doi: 10.12965/jer.1735048.524. eCollection 2017 Oct.

    PubMed 29114536

  • Scott WR. Conflicting levels of rationality: regulators, managers, and professionals in the medical care sector. J Health Adm Educ. 1985 Spring;3(2 Pt 2):113-31. No abstract available.

    PubMed 10276329

  • Marinelli V, Danzi OP, Mazzi MA, Secchettin E, Tuveri M, Bonamini D, Rimondini M, Salvia R, Bassi C, Del Piccolo L. PREPARE: PreoPerative Anxiety REduction. One-Year Feasibility RCT on a Brief Psychological Intervention for Pancreatic Cancer Patients Prior to Major Surgery. Front Psychol. 2020 Mar 5;11:362. doi: 10.3389/fpsyg.2020.00362. eCollection 2020.

    PubMed 32194490

  • Lundstrom CJ, Foreman NA, Biltz G. Practices and Applications of Heart Rate Variability Monitoring in Endurance Athletes. Int J Sports Med. 2023 Jan;44(1):9-19. doi: 10.1055/a-1864-9726. Epub 2022 Jul 19.

    PubMed 35853460

  • Leite MR, Ramos EM, Kalva-Filho CA, Rodrigues FM, Freire AP, Tacao GY, de Toledo AC, Cecilio MJ, Vanderlei LC, Ramos D. Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD. Respirology. 2015 Feb;20(2):273-8. doi: 10.1111/resp.12424. Epub 2014 Nov 9.

    PubMed 25381699

Questions about this trial

What is this clinical trial studying?

A study testing Multimodal prehabilitation program in people with Cancer Surgery, run by Università Vita-Salute San Raffaele at 4 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Fabio Guarracino, Dr (+393281652528, f.guarracino@ao-pisa.toscana.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assess the impact of prehabilitation on heart rate variability (time frame: Preoperative). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06744413, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.

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