Clinical trial NCT04375917: Is Reduced Hypoxia Through a Robot Intervention, Associated With Sensory and Emotional Descriptions of Dyspnea, Anxiety, Depression, Symptom Burden and Anxiolytics
Official title: Is Reduced Hypoxia Through a Robot Intervention, Associated With Sensory and Emotional Descriptions of Dyspnea, Anxiety, Depression, Symptom Burden and Anxiolytics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COPD
Dyspnea
Anxiety
Depressive Symptoms
Hypoxia
Closed-Loop Communication
Lead sponsor: Copenhagen University Hospital, Hvidovre
Sponsor class: OTHER
First posted: 2020-05-06
Enrollment: 157
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label randomized controlled parallel study
Primary purpose: TREATMENT

Brief summary: Chronic Obstructive Pulmonary Disease (COPD) is associated with high morbidity and mortality. The Danish Lung Association estimates that 320,000 Danes live with COPD, of which approximately 50,000 with severe COPD. In 2017, records showed that 23,979 admissions in Denmark were related to COPD; of these patients, about 20% were readmitted 2-30 days after discharge. The main symptom is dyspnea, which is often accompanied by anxiety. Primary treatment is; oxygen, bronchiolitis, prednisolone, morfin, NIV, and anxiolytics.

Researchers at Hvidovre Hospital have developed an oxygen robot that continuously monitors the patient's SaO2 (oxygen saturation) and automatically administrates the oxygen depending on it. The preliminary results show that patients with robot-administrated oxygen were within defined SaO2 range in 85.7% of the time versus 46.6% when oxygen was nurse-administrated. The research was conducted as a multicentre Randomized Controlled Trial (RCT)focusing on physiological end-points.

There is a lack of knowledge about the patient perspective of treatment with the oxygen robot.

The purpose of this study is:

1. To examine the association between robot-administered oxygen and patients' perception of dyspnoea, including the emotional response in the form of anxiety and depression

The perspective is to be able to provide a holistic response to whether robot administered oxygen can be a better method of treating and alleviating dyspnoea.

Detailed description: Chronic Obstructive Pulmonary Disease (COPD) is a high prevalence disease and is associated with high morbidity and mortality worldwide. In 2017, there were 23.979 COPD related admissions in Denmark, approximately 10% died during hospitalization, while 20% of survivors were readmitted between day 2-30 after discharge. Patients with COPD often experience long disease trajectories characterized by a substantial burden of symptoms, impaired functional status, multiple admissions and thereby reduced quality of life. The cardinal symptom dyspnea is associated with hypoxemia, anxiety and depression. Evidence shows that depression is a significant risk factor for disabling dyspnea, while risk of anxiety increases with the severity of Dyspnea.

The prevalence of anxiety and depression is indicated to lie between 10%-55% and 10%-86% in patients hospitalized with COPD in exacerbation . Patients with COPD have an 85% increased risk of developing anxiety compared to a matching control group without COPD. The prevalence of anxiety is 10 times higher among patients with COPD than in the background population and are strongly associated with the risk of hospitalization, long admissions, readmissions and death. Anxiety and depression are often treated with benzodiazepines which have a respiratory suppressive effect. Consumption of benzodiazepines increases disease progression, and studies have shown that 31.7% of patients with COPD have a benzodiazepine consumption and that 9% initiate a new benzodiazepine ordination in conjunction with an exacerbation. The evidence that oxygen prevents disease progression and mortality is consistent, but there is a lack of knowledge about whether oxygen, can reduce the intensity of dyspnea in patients with COPD. In the acute phase of an exacerbation the oxygen flow is titrated to achieve a SaO2 between 88-92%. Keeping patients with COPD within the given SaO2 range is essential because too low SaO2 can induce tissue damage, heart overload and difficulty concentrating, while hyperoxaemia can inhibit respiration and increase the risk of hypercapnia, acidosis and the need for ventilatory support in the form of Non-invasive Ventilation (NIV). In clinical practice, oxygen flow is administered and titrated, via aggregates, by nurses based on point observations, with the risk of patients being outside optimal SaO2 range, between observations. To improve practice, a group of researchers at Hvidovre Hospital has developed an oxygen robot, called O2matic, which continuously monitors the patient's SaO2 and automatically administrates oxygenflow according to it. O2Matic has been tested in a randomized controlled trial (RCT) in 2018. Patients admitted with an exacerbation of COPD and hypoxemia (SaO2 ≤ 88%) was included (N = 19). The design was crossover and patients were allocated to either 4 hours of manual oxygen administration via nurse followed by 4 hours of oxygen administration via O2Matic, or vice versa. The study showed that patients with O2matic controlled oxygen administration were within defined SaO2 range in 85.7% of the time versus 46,6% of the time when the oxygen was controlled and administrated by a nurse . These results are in consensus with a former Canadian study testing an alternative oxygen robot (FreeO2). The two RCT Studies provide evidence to investigate robot-administered oxygen therapy for inpatient patients with exacerbation of COPD in a larger multicenter Randomized Controlled Trail.

Dyspnea is defined as; "A subjective experience of breathing discomfort that consist of qualitatively distinct sensations that vary in intensity". The experience of dyspnea is a product of a physical perception based on signals from the body to the brain followed by the cognitive processing of these into an emotional experience. Dyspnea is thus an emotional and sensational experience based on perceptual afferent feedback from various respiratory receptors. Up to 16 possible mechanisms are involved in the process . Given the above, dyspnea is a complex symptom, mainly induced by the body's attempts to obtain homeostasis, when subjected to hypoxemia. Despite this dyspnea is not the same as hypoxemia, as it has not been clearly demonstrated that reduced hypoxemia, by oxygen therapy also reduces Dyspnea. However, there are indications in the literature that oxygen therapy can reduce the experience of dyspnea. A significant barrier to the use of oxygen therapy as an intervention on fragmentary dyspnea in patients with COPD is the risk of hypercapnia and acidosis. Oxygen therapy administrated according to saturation in a closedloop-feedback-system by a robot, could potentially be an intervention to relieve fragmentary dyspnea in patients with COPD. International guidelines show that dyspnea is not treated consistently nor effectively in the advanced stages of the disease.

Opioids are one of the most widely used agents in the treatments of dyspnea. Opioids suppress' respiration and treatment should be balanced to avoid respiratory depression. Guidelines points out the importance of identifying and graduate the intensity of dyspnea in clinical practice, without indicating any superior instruments to achieve this. Majority of instruments developed, describe dyspnea in relation to activity. As COPD progress, dyspnea intensifies and patients will become more inactive and often live a sedentary life. Few questionnaires measure the sensory and emotional domains of dyspnea independently of activity and diagnose. One is the multidimensional Dyspnoea profile (MDP) that has recently been translated into Danish. In order to reduce symptom burden, length of hospital stay, number of readmissions and mortality, new knowledge and more effective methods for treating and alleviating dyspnea and the associated anxiety and depression are needed in patients with COPD. Studies investigating the effect of oxygen therapy, including time with and degree of hypoxemia, in hypoxemic patients experiencing dyspnea, anxiety or depression during hospitalization with acute exacerbation, could not be identified. Because O2matic provides a new and unique opportunity to reduce and illuminate time with hypoxemia during hospitalization and patient's subjective experience of the sensory and emotional aspects of dyspnea can be reported on a validated questionnaire via MDP, researchers now have an option to investigate if a robot intervention, that reduces time with hypoxemia, has an effect on dyspnea in patients admitted with a exacerbation of COPD. Furthermore, investigators want to examine whether this intervention alters the consumption of opioids and benzodiazepines.

Primary hypothesis. Reduced time with hypoxia, via active differentiated oxygen supply determined by visible monitored saturation, affects the sensory and emotional response to dyspnea, anxiety, depression and consumption of medication.

Primary objective:

To investigate whether there is an association between time with hypoxemia and dyspnea, described by the Sensory Question (SQ) scale and A2 scale of MDP, in patients admitted with an exacerbation of COPD and a need for oxygen therapy Secondary hypothesis 1 The intensity of dyspnea, anxiety, depression and respiratory symptom burden is dependent on time with and degree of hypoxemia

Secondary objective 1:

To investigate whether there is an association between time with-and degree of hypoxemia and respectively dyspnea, anxiety, depression and symptom burden Secondary hypothesis 2 Reduced time with-and degree of hypoxemia reduces consumption of anxiolytics expressed in Mg

Secondary objective 2:

To investigate whether there is an association between time with-and degree of hypoxemia and anxiolytics represented as Benzodiazepines, morphine and "Oramorph" drops

Eligibility criteria: Inclusion Criteria:

* • COPD veryfied by Forced Expiratory Volume in 1 sec (Fev1) divided by forced Vital Capacity (FVC)\< 0,70

  * Admission due to exercabation in COPD
  * COPD exacerbation and pneumonia can be included
  * Expeted duration of admission \>48 hours
  * Need for oxygen supplementation (SpO2\<= 88% in room air) Cognitive able to participate in the study
  * Willing to participate and give informed consent

Exclusion Criteria:

* • Need or anticipated need for mechanical ventilation ( Intermittent continuous Positive Airway Pressure (CPAP) is allowed)

  * Major comorbidities causing hypoxemia (cancer, heart disease, pulmonary embolia)
  * Asthma or other respiratory conditions requiring higher SpO2 than normal for COPD Pregnancy
  * Cognitive barrierers for participation

Primary outcomes:
measure: Global dyspnea measured on scale A1 on multidimensional Dyspnea Profile (MDP)
timeFrame: 3 days
Secondary outcomes:
measure: The emotional dimension of dyspnea
timeFrame: 3 days
measure: The sensory dimension of dyspnea
timeFrame: 3 days
measure: Current Dyspnea
timeFrame: 3 days
measure: Accumulated Dyspnea
timeFrame: 3 days
Other outcomes:
measure: Respiratory symptom intensity
timeFrame: 3 days
measure: Anxiety symptoms
timeFrame: 3 days
measure: Depressive symptoms
timeFrame: 3 days
measure: prednisolon
timeFrame: 3 days
measure: Antibiotics
timeFrame: by inclusion
measure: Phenergan
timeFrame: 3 days
measure: Serenase
timeFrame: 3 days
measure: Morfin
timeFrame: 3 days
measure: Methadon
timeFrame: 3 days
measure: Oramorph
timeFrame: 3 days
measure: Tradolan
timeFrame: 3 days
measure: Kodein
timeFrame: 3 days
measure: Lorazepam
timeFrame: 3 days
measure: Oxazepam
timeFrame: 3 days
measure: Diazepam
timeFrame: 3 days
measure: Imoclone
timeFrame: 3 days
measure: Zolpiclone
timeFrame: 3 days
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg University Hospital
city: Copenhagen
country: Denmark
facility: Hvidovre University Hospital
city: Copenhagen
country: Denmark
facility: Herlev University Hospital
city: Copenhagen
country: Denmark
facility: Gentofte University Hospital
city: Frederikssund
country: Denmark
facility: Nordsjællands Hospital
Study officials:
affiliation: Hvidovre University Hospital, Kettegaard alle
name: charlotte Sandau Bech, MScHS
role: PRINCIPAL_INVESTIGATOR
affiliation: Hvidovre University Hospital
name: Thomas Jørgen Ringbæk, PhD, associated professor
role: STUDY_CHAIR
References: