Combined Rehabilitation and Nutritional Support vs. Standard Care in In-Hospital Endocarditis Treatment

NCT ID: NCT06563609

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-19
• Study Completion Date: 2025-12-07

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).

Conditions

Infective Endocarditis; Endocarditis, Bacterial; Infection; Heart; Bacteremia; Cardiac Rehabilitation; Nutrition Intervention; Physical Therapy; Probiotic Intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Integrated Physical Therapy and Nutritional Support with Probiotic Saccharomyces boulardii

Intensive physical therapy + individualised nutritional support + administration of probiotic yeast saccharomyces boulardii

Group Type: ACTIVE_COMPARATOR

Intensive physical Therapy

Intervention Type: BEHAVIORAL

Tailored exercise programs supervised by trained physiotherapists, focusing on improving cardiorespiratory fitness, strength, and functional capacity.

Probiotic treatment

Intervention Type: DIETARY_SUPPLEMENT

Administration of probiotic yeast Saccharomyces boulardii twice daily

Individualised Nutritional Support

Intervention Type: BEHAVIORAL

Personalized nutritional plans guided by a dietitian, addressing malnutrition and caloric/protein deficiencies with daily caloric intake adjustments and supplements if necessary based on the EFFORT trial.

A combined Intensive physical Therapy and individualised Nutritional Support intervention

Intensive physical Therapy + Individualised Nutritional Support

Group Type: ACTIVE_COMPARATOR

Intensive physical Therapy

Intervention Type: BEHAVIORAL

Tailored exercise programs supervised by trained physiotherapists, focusing on improving cardiorespiratory fitness, strength, and functional capacity.

Individualised Nutritional Support

Intervention Type: BEHAVIORAL

Personalized nutritional plans guided by a dietitian, addressing malnutrition and caloric/protein deficiencies with daily caloric intake adjustments and supplements if necessary based on the EFFORT trial.

Administration of probiotic yeast Saccharomyces boulardii

Administration of probiotic yeast Saccharomyces boulardii

Group Type: ACTIVE_COMPARATOR

Probiotic treatment

Intervention Type: DIETARY_SUPPLEMENT

Administration of probiotic yeast Saccharomyces boulardii twice daily

Control group

Standard hospital care

Group Type: PLACEBO_COMPARATOR

Standard hospital care

Intervention Type: OTHER

Patients will receive standard hospital care

Interventions

Intensive physical Therapy

Tailored exercise programs supervised by trained physiotherapists, focusing on improving cardiorespiratory fitness, strength, and functional capacity.

Intervention Type: BEHAVIORAL

Probiotic treatment

Administration of probiotic yeast Saccharomyces boulardii twice daily

Intervention Type: DIETARY_SUPPLEMENT

Individualised Nutritional Support

Personalized nutritional plans guided by a dietitian, addressing malnutrition and caloric/protein deficiencies with daily caloric intake adjustments and supplements if necessary based on the EFFORT trial.

Intervention Type: BEHAVIORAL

Standard hospital care

Patients will receive standard hospital care

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johannes Grand

OTHER

Sponsor Role: lead

Responsible Party

Johannes Grand

MD, PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Johannes Grand, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Copenhagen University Hospital Amager-Hvidovre, Department of Cardiology

Locations

Hvidovre Hospital

Hvidovre, , Denmark

Countries

Denmark

Other Identifiers

ENDOCARE-001

Identifier Type: -

Identifier Source: org_study_id