Clinical trial NCT06563609: Combined Rehabilitation and Nutritional Support vs. Standard Care in In-Hospital Endocarditis Treatment
Official title: Combined Physical Rehabilitation and Individualized Nutritional Support Versus Standard of Care During In-hospital Endocarditis Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infective Endocarditis
Endocarditis, Bacterial
Infection; Heart
Bacteremia
Cardiac Rehabilitation
Nutrition Intervention
Physical Therapy
Probiotic Intervention
Keywords: Infective endocarditis
Endocarditis team
Physical Therapy
Individualized Nutritional Support
Probiotic yeast Saccharomyces Boulardii
Cardiac rehabilitation
Lead sponsor: Copenhagen University Hospital, Hvidovre
Sponsor class: OTHER
First posted: 2024-08-21
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated, randomized, single-center, 2-by-2 factorial clinical trial with co-enrolment into two different non-pharmacological interventions.

* A combined Intensive physical Therapy and individualised Nutritional Support intervention and administration of probiotic yeast Saccharomyces boulardii
* A combined Intensive physical Therapy and individualised Nutritional Support intervention and NO administration of probiotic yeast Saccharomyces boulardii
* Administration of probiotic yeast Saccharomyces boulardii and NO Intensive physical Therapy and individualised Nutritional Support.
* NO administration of probiotic yeast Saccharomyces boulardii and NO Intensive physical Therapy and individualised Nutritional Support. Patients will receive standard hospital care
Primary purpose: SUPPORTIVE_CARE

Brief summary: Infective endocarditis (IE) is associated with high morbidity and mortality. Patients with IE are affected by a lengthy hospitalization, leading to physical deconditioning and a rapid decline in physical fitness, muscle mass and strength. Moreover, prolonged antibiotic regimens frequently result in nausea, antibiotic-associated diarrhea and Clostridioides difficile (C.difficile) intestinal infections that further negatively affect patient health. These physical challenges are further exacerbated by the negative impact on mental health, increasing the overall burden of the illness. Implementing a targeted rehabilitative strategy in the hospital setting may therefore improve patient care including physical health and overall quality of life during hospitalization.

Detailed description: BACKGROUND:

Infective endocarditis (IE) is a severe infection of the heart's inner lining, typically the valves, carrying high risks of acute heart failure and death. Patients often face extended hospitalizations (up to six weeks or longer) for intravenous antibiotic treatments, with 30-50% requiring urgent valve surgery. The incidence of IE is 8-10 per 100,000 person-years and rising due to aging populations and increased use of cardiac implantable devices, accounting for 650-700 cases annually in Denmark. Without treatment, mortality is nearly 100%, and with treatment, it ranges from 5-30% during the initial hospitalization, influenced by factors such as infection site, causative agent, age, and comorbidities.

IE significantly impacts patients' health due to prolonged hospitalization. Many experience rapid physical decline, including reduced cardiorespiratory fitness, strength, and overall fitness, caused by bed rest, malnutrition, and limited activity. Recovery is often difficult, with worsening physical, mental, and emotional states. The POET trial found poor self-rated health triples mortality risk. Up to 35% of patients do not return to work, and 65% face readmission within a year. Long hospital stays also increase the need for nursing home care.

Malnutrition is common in IE patients, raising risks of death, illness, and impairment. Acute illness amplifies nutritional deficits, worsening muscle wasting and overall health. The EFFORT trial showed early nutritional support reduces mortality and complications, yet no randomized studies have addressed nutrition in IE patients.

Intravenous antibiotics add distress, often causing nausea, diarrhea, and C. difficile infections. Probiotics like S. boulardii show promise in preventing these side effects.

Cardiac rehabilitation has proven benefits for other heart conditions, improving exercise capacity, quality of life, and reducing readmissions. However, evidence is limited for in-hospital IE rehabilitation. Tailored, supervised programs during hospitalization could address physical and mental health needs, improving overall recovery and quality of life.

PRIMARY AIM:

To investigate the effectiveness of individualized physical rehabilitation and nutritional support designed to reduce physical deconditioning and prevent treatment-related harms thus ultimately improving mental health in patients hospitalized with endocarditis.

HYPOTHESES:

Within a 2-by-2 factorial design, a patient-centered, individualized, and adaptable physical rehabilitation and nutritional plan during lengthy hospitalization will improve mental health more than standard care.

Furthermore, in the same factorial framework, a probiotic supplement during antibiotic-treatment will decrease the rate of antibiotic-associated diarrhea compared to no probiotic supplement.

NUTRITIONAL SUPPORT:

In the intervention group, nutritional screening and support begin within 24 hours of randomization. Individualized nutritional plans are developed based on the NRS 2002 protocol and 2018 international guidelines. A dietitian sets energy requirements using the weight-adjusted Harris-Benedict equation and establishes protein intake targets between 1.2-1.5 g/kg of body weight, adjusting to 0.8 g/kg for patients with acute renal failure.

Patients are screened for risk of refeeding syndrome with routine blood tests, including magnesium, phosphate, and other relevant biomarkers (e.g., bilirubin, creatinine, albumin, electrolytes, etc.). The initial dietary plan includes hospital-provided meals, snacks from an "à la carte" menu, and oral nutritional supplements (ONS). Daily food records monitor intake, and if patients fail to meet 75% of caloric and protein targets for three consecutive days-or earlier based on clinical judgment-escalation to enteral tube feeding or parenteral feeding is initiated.

INDIVIDUALLY PLANNED PHYSICAL EXERCISE BY AN INTERDISCIPLINARY TEAM LEAD BY A SPECIALIZED REHABILITATION PHYSIOTHERAPIST:

The ENDOCARE team, consisting of a cardiologist, nurse, and physiotherapist, optionally involving a family member, will meet with the patient the first weekday after inclusion to design a personalized exercise regimen. This regimen accounts for comorbidities, performance status, disease severity, and support resources. Weekly meetings with the team will address patient concerns and ensure optimal care.

Exercise Modalities

Patients will participate in Intensive Exercise to reduce deconditioning and enhance well-being, focusing on:

Progressive Resistance Exercise: Major muscle groups (e.g., leg presses, arm rows, arm pushes) are targeted with 2-3 sessions/week, using stationary equipment or elastic bands. Training follows a linear progression (3 sets per exercise starting at 15 ± 2 RM, progressing to 10 ± 2 RM) and integrates principles like range of motion and time under tension.

Cardiovascular Exercise: Sessions involve 20 minutes of moderate-intensity exercise (Borg RPE 12-14) 3-4 times/week, using arm ergometers or stationary beds. Intensity and structure (continuous or interval) are adjusted based on patient preference.

Physical Activity Daily physical activity, guided by Danish recommendations (10,000 steps/day), is encouraged using a gradual progression model (e.g., PACE-UP). Activity monitoring is supported by SENS motion accelerometers, with data transferred to a smartphone app. Depending on funding, tablets may provide real-time feedback on activity levels near patient beds.

Control Group Patients in the control group receive standard hospital care, including an initial physiotherapist assessment and 1-2 supervised or self-managed exercise sessions per week.

Risks Potential risks include musculoskeletal injuries (e.g., strains, sprains), fatigue, and overtraining.

GUIDE FOR PROBIOTIC ADMINISTRATION:

In the intervention group, S. boulardii treatment begins at inclusion. Patients will receive Sacchaflor capsules (Pharmaforce Aps), containing S. boulardii (5×10\^9 DBVPG 6763 strain) and mannan oligosaccharide (MOS), a supplement derived from Saccharomyces cerevisiae. The capsules are administered twice daily until the end of antibiotic treatment. If the patient is discharged with continued antibiotics, S. boulardii will be used for up to 30 more days.

In the control group, no probiotics will be given for 30 days post inclusion.

Possible side effects include gastrointestinal disturbances (e.g., flatulence, bloating, constipation) and, rarely, fungemia or allergic reactions).

Eligibility criteria: INCLUSION CRITERIA

* Clinical diagnosis of left-sided (native, prosthetic, or culture-negative) bacterial infective endocarditis mandating iv antibiotic treatment, including Cardiac Implantable Electronic Devices infections, irrespective of cause and location as defined by the ESC modified Duke Criteria
* Age ≥ 18 years

EXCLUSION CRITERIA

* Hemodynamic instability (defined as a systolic blood pressure \<90 mmHg and lactate \>2.2 mmol/l measured in an arterial blood gas.
* Expected to be discharged within 3 days
* Immunocompromised due to severe combined immunodeficiency, HIV, or hematological malignancy
* Fungal endocarditis
* Pregnancy
* Unwilling or unable to sign or understand informed consent

Primary outcomes:
measure: Mental health (MH) measured by the standardized Short Form 36 (SF-36)
timeFrame: 30 days
Secondary outcomes:
measure: Change in number of sit and stand in 30 seconds from baseline to 14 days
timeFrame: 14 days
measure: Quality of life from EQ-5D
timeFrame: 14, 30, and 90 days follow-up
measure: Days alive without diarrhea
timeFrame: 30 days in hospital and 90 days out of hospital
measure: Days alive and out of hospital
timeFrame: 30 day in hospital, and 90 day out-of-hospital
measure: All-cause mortality
timeFrame: 30 days
Other outcomes:
measure: Albumin Measurement
timeFrame: 14 days
measure: The occurrence of C. difficile infection
timeFrame: 14 days and 30 days
measure: NT-proBNP
timeFrame: 14 days after admission
measure: Left ventricular ejection fraction
timeFrame: 14 days
measure: SENS motion
timeFrame: First 7 days
measure: Self-rated Hospital Anxiety and Depression Scale (HAD)
timeFrame: 14, 30, and 90 days follow-up
measure: HbA1c
timeFrame: Day 14
measure: Lipids
timeFrame: Day 14
measure: Number of patients at risk of malnutrition
timeFrame: Day 14
measure: Number of patients getting daily average of at least 75% of the caloric and protein targets on day 4
timeFrame: Day 14
measure: Number of patients required for enteral tube feeding or parenteral feeding
timeFrame: Day 14
measure: Grip strength
timeFrame: 14, 30, and 90 days
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
Study officials:
affiliation: Copenhagen University Hospital Amager-Hvidovre, Department of Cardiology
name: Johannes Grand, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: