Symptoms and General Pathology

All Conditions

Postoperative Complications

Christian S Meyhoff, MD, PhD

Eske K Aasvang, MD, DMSci

Helge B Dissing, PhD

Camilla L Duus, MB

Postoperative observation of patients is based on the Early Warning Score (EWS). By using continuous wireless monitoring of vital parameters it may be possible to predict the risk of complications after abdominal cancer surgery. The object of this pilot study is to test the equipment and methods for the next phases. Patients will be monitored for 4 days postoperatively and data is analyzed retrospectively. Vital parameters are monitored with ECG, blood pressure monitor and pulseoximetry.

In the analysis the investigators will compare the results from the continuous monitoring to the measurements made by the nurses and registered in the EWS. The primary outcomes for the pilot study are the frequency of measurements resulting in a single parameter score of 3 according to the EWS algorithm.

Wireless Assessment of Respiratory and Circulatory Distress; A Pilot Study

All data from the monitoring will be analyzed using the thresholds from the EWS algorithm and will be sorted into relevant categories. The following thresholds are used:

Bradycardia: pulse \< 41 bpm Tachycardia: pulse \> 130 bpm

Bradypnea: \< 9 breaths/min Tachypnea: \> 24 breaths/min

Hypotension: Systolic blood pressure \< 91 mmHg Hypertension: Systolic blood pressure \> 219 mmHg

Hypoxemia: arterial oxygen saturation \< 92 %

Rigshospitalet, Denmark

Technical University of Denmark

Bispebjerg Hospital

Research Assistant

Neoplasms

Neoplasms, Second Primary

Blinded data collection by the WARD-CSS without vital signs and active alerts displayed to the ward staff

Monitoring by the WARD-CSS including vital signs and active alerts relayed to the nurses' smartphones during hospitalization

Patients' continuously monitored vital signs will be recorded via a bedside tablet device (data not visible).

The clinical staff will have access to the continuously monitored vital signs through a mobile device (smart phone) with a purpose-built app-based GUI displaying vital sign status and summaries, alarms, and device connectivity. The GUI will alert the clinical staff (acoustic and visual signals) when any of the predefined thresholds for deviating vital signs are exceeded.

WARD-CSS

Jesper Mølgaard, PhD

Eske K Aasvang, DMSc

Christian S Meyhoff, PhD

Katja B L Glud, RN

Søren Kjær, MD

The primary objective of this study is to determine the effect on complication severity of using a clinical monitoring system with automatic vital sign alerts in addition to routine monitoring versus routine monitoring alone in high-risk postoperative cancer patients within 30 days after surgery.

Other objectives include documentation of the severity of complications within seven days of surgery, frequency of serious adverse events, mortality, length of stay and delay of planned chemotherapy.

The primary objective of this study is to determine the effect on complication severity of using the WARD-CSS with automatic alerts in addition to routine monitoring versus routine monitoring alone in high-risk postoperative cancer patients within 30 days after surgery.

This study is a multicenter randomized controlled trial (RCT). Patients are randomly assigned to one of two parallel monitoring groups: (1)Intervention group - Monitoring by the WARD-CSS including vital signs and active alerts relayed to the nurses' smartphones during hospitalization. (2)Control group - Blinded data collection by the WARD-CSS without vital signs and active alerts displayed to the ward staff.

Both groups will receive routine vital signs monitoring (i.e. manual spot-checks) using the regional EWS/TOKS system according to current standards of care at the participating hospitals in the Capital Region or the Central Denmark Region.

The study is a collaboration between Rigshospitalet, Bispebjerg and Frederiksberg Hospital, and Hvidovre Hospital.

Patients will be recruited from abdominal (gastrointestinal, gynecological, or urological) surgery wards at the study sites.

Patients will be randomized post-surgery at the postoperative units/ post-anesthesia-care unit or after arrival at the ward. Continuous wireless monitoring (i.e., unblinded with alerts or blinded) will commence immediately after randomization in the study.

Only randomized patients will be included in the study population. Drop-outs prior to randomization will not be part of the study population.

The first 14 days of active enrollment at each new study site that has not previously used WARD-CSS will be used to align study procedures, verify system connectivity, etc. During this period, up to ten patients at each study site will be enrolled to be monitored similar to the intervention group. These run-in patients will not be randomized and will not be considered part of the study population.

Participants will not be given information on group allocation. Care-providers will not be blinded, due to having to carry out the intervention.

Investigator will not be blinded to carrie out roles such as safety surveillance, error-solving and quality assurance.

Outcome assessor will be blinded to study allocation.

Postoperative Complications in Cancer Patients Monitored With Intelligent Continuous Monitoring System

Postoperative Complications in Cancer Patients Monitored With Intelligent Continuous Monitoring System Versus Standard of Care - a Randomized Clinical Trial

Frequency of severe clinical complications Defined as any complication fulfilling the Clavien-Dindo classification ≥2

Number of patients with unplanned admission to the intensive care unit after surgery

Any unplanned surgical reintervention of any kind.

Re-admission for any reason related to the operation or their respective cancer

Health-economic cost-effectiveness. Data will be collected from all available health care databases in the danish public health care system (ie. use of general practitioners, hospital admissions, hospital registered costs and services, work-leave periods) for a maximum follow up period of 2 years after primary surgery and analyzed when full datasets are available

Severity of complications assessed by the Comprehensive Complication Index (CCI) score. Complications are defined according to internationally agreed definitions of complications.

CCI can take on numerical values in the scale from 0 (no complications) to 100 (patient deceased).

Frequency of Serious adverse events (SAE) SAE is defined by ICH-GCP criteria as: Any unfavourable medical occurrence that

* results in death
* is life-threatening
* requires inpatient hospitalisation or prolongation of existing hospitalisation
* results in persistent or significant disability/incapacity
* is a congenital anomaly/birth defect

For patients scheduled to recieve postoperative chemotherapy, this is the time from surgery to initiation of post-operative adjuvant chemotherapy

For patients scheduled to recieve postoperative chemotherapy, this is the number of patients that complete their post-operative adjuvant chemotherapy.

Hvidovre University Hospital

Principal investigator

Blood and Lymph Conditions

Syndrome

Hematologic Neoplasms

Cytokine Release Syndrome

Hematologic Diseases

Systemic Inflammatory Response Syndrome

Inflammation

Shock

All Drugs and Chemicals

Immunomodulating Agents

alarms will notify the health personel that there is an abnormal vital sign, and the personel will act accordingly.

Heart rate and respiratory rate is measured using Isansys lifetouch (Isansys Lifecare, Oxfordshire, UK), single-lead ECG monitor. An ECG is recorded as a 10-second segment every minute. Heart rate is derived once per minute from the R-R interval, and similarly, the RF is calculated from the changes in thoracic impedance once per minute. Blood pressure is monitored with either Meditech BlueBP-05 (Meditech Ltd., Budapest, Hungary) or A\&D TM-2441 (A\&D company Ltd., Tokyo, Japan). Both are non-invasive oscillometric, cuff-based blood pressure monitoring devices. Peripheral oxygen saturation was measured with NonIn WristOx 3150 (Nonin Medical Inc., Minnesota, USA) pulse oximeter, which is a photoplethysmograph with a sampling frequency of 75 Hz.

WARD

Sandra Egedie Lyby Taylor Pitter, MD

Eske K Aasvang, Professor

Aims

* To identify patients that should remain admitted in hospital for more intense surveillance because of high risk for development of clinical complications
* Expand the understanding of the interactions between physiology and immunology for the design of future projects and general knowledge Hypothesis Development of a risk model based on a combination of physiological and immunological parameters can contribute to early detection of patients at risk for clinical complications after anti-cancer treatment.

Patients going through medical or surgical cancer treatment have a joined risk for clinical complications after treatment. Complications are often discovered too late because patients are checked on periodically during hospitalization, but it is estimated that at least 40% of these complications can be prevented if they are discovered in time. Yet this requires the development of new methods for patient monitoring.

Immunologic and physiologic monitoring show promising results, because activation of the immune system is either a consequence to a clinical complication (e.g. infection), or on its own pathological (e.g. systemic inflammatory response syndrome (SIRS), and cytokine release syndrome (CRS)).

Therefor the purpose of this study is to combine three research projects to further the understanding physiological and immunological pathways, and attempt to improve patient monitoring, in hopes of raising patient care levels and enhance clinical outcomes. The research projects are as follows:

* WARD (''wireless assessment of respiratory and circulatory distress''). A continuous wireless surveillance of patient vital signs in real time. Time stamped data facilitate comparing of patterns of more than one vital sign. WARD clinical support system is developed and tested on \> 3.000 patients with more than 250.000 hours of recordings since 2016.
* Phase one unit. An acknowledged clinical research unit where advanced cancer immune therapy is administered safely and under close observation. Thus, patients can safely be admitted for days to weeks and supervised for development of any clinical complications which make intervention possible in time. The unit has a high patient volume which guarantees a high inclusion rate and is a unique opportunity to conduct advanced project in a controlled environment, which is essential for the project machine-learning methodology
* TruCulture and Duraclone. High dimensional immune phenotyping as well as standardised testing system study the immune function in blood after ex vivo stimulation from selected host response pathways, and measuring of plasma levels for pro- and anti-inflammatory markers for systemic inflammation (TNF-alpha, interleukins, CRP etc.) The project group has until now focused on the surgical trauma as a standardized stimulation of the immune system, where development of clinical complications can be related to measurements before and after the trauma. This stands in opposition to most other illnesses, where patients are first seen by a healthcare worker when the illness has occurred. In this joined project the three projects previously mentioned will be combined to make a unique description of the development of clinical complications or the absence hereof in relation to treatment of haematological malignancies with antigen receptor stimulation.

The project will be based on the previous decades' development of anti-cancer treatments, where focus has shifted from chemotherapy to biological targeted treatments. An example hereof is small molecules that affects intracellular pathways (Kinase inhibitor) and antibody treatments targeting cancer specific surface molecules \[7\]. In the past five years has the development taken a rapid leap with some kinds of immune therapy, especially chimeric antigen receptor T-cell treatment (CART) and T-cell engaging bispecific antibodies (BsAbs). With these new treatment options comes other side effects and these T-cell antigen treatments are no exception. The most common side effect to CART and BsAbs is cytokine release syndrome (CRS). It is seen in \> 50% of the treated patients within the first month of treatment. CRS is a hyperinflammatory syndrome, that occurs when a series of cytokine sand chemokines are released by T-cell activation and -recruitment. The syndrome ranges from monosymptomatic fever (grade 1) but is often accompanied by hypoxia and/or hypotension (grade 2). CRS grade three to four include affection of vital organs, which can possibly develop into an irreversible condition. The treatment entails antipyretics, adrenocorticotropic hormone in the early phases, and more advanced monoclonal antibodies in cases of CRS grade two to four. The definition and grading of CRS is based on the presence of fever and the grade of hypoxia and hypotension, thus based on thresholds for vital signs and without the use of immunologic markers. The early detection of signs for CRS will enable early onset of treatment which subsequently can halt the development of the condition. Risk factors for the development of severe CRS are described but the predictive value is low. The level of inflammatory cytokines is correlated to the severity of CRS but these cytokines (CRP, IL-6 etc.) significantly increase hours to days after the development of the clinical syndrome, which make not suitable for evaluating the need for hospitalization and/or treatment for CRS. Early onset markers for the development of CRS are therefor clinical signs of systemic inflammation, e.g. rise in temperature, decrease in blood pressure, desaturation, and likely tachycardia. Thus, the combination of CART and BsAbs treatment, the WARD project and immune profiling is a unique opportunity to improve this field and potentially have great impact on patients' outcome.

Early Detection of Complications During Immunotherapy for Haematological Malignancy

Early Detection of Complications During Immunotherapy for Haematological Malignancy - Description of Associated Vital Signs and Immune Responses

Data will be shared if apporiate use and reasons are presented to the study personell

characterized by TruCulture before anti-cancer treatment

recorded with WARD equipment (e.g. hypotension, desaturation, tachycardia, etc.) post anti-cancer treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Wireless Assessment of Respiratory and Circulatory Distress; A Pilot Study	NCT03102619	Abdominal Cance... Postoperative C... Respiratory Com... Circulatory; Co...		65 Years -	Bispebjerg Hospital
Postoperative Complications in Cancer Patients Monitored With Intelligent Continuous Monitoring System	NCT06269198	Postoperative C... Cancer, Treatme...	WARD-CSS	18 Years -	Rigshospitalet, Denmark
Early Detection of Complications During Immunotherapy for Haematological Malignancy	NCT06377059	Hematologic Can... CRS - Cytokine ...	WARD	18 Years -	Rigshospitalet, Denmark
Postoperative Complications in Cancer Patients Monitored With Intelligent Continuous Monitoring System	NCT06269198	Postoperative C... Cancer, Treatme...	WARD-CSS	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for wireless monitoring