Infectious EndocarditisPhase 2ENDOHOTNCT04691440
Hyperbaric Oxygen Treatment in Humans With Gram Positive Cocci Endocarditis
A Phase 2 study testing Hyperbaric oxygen in people with Infectious Endocarditis, run by Ole Hyldegaard at 1 site in Denmark.
Trial summary
Infectious endocarditis (IE) is defined as an infection anywhere on the endocardium, most often localised to the cardiac valves. It is an infection with an increasing incidence and in Denmark with 6-700 new cases annually. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Infectious Endocarditis
- What is being tested?
- Hyperbaric oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Dec 2019to 31 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Left sided IE with gram positive cocci.
- IE has been diagnosed according to modified Duke Criteria.
- Patients must be stable, by means of no need for hemodynamic pressure support.
- The patient must be able to be seated for the 1.5 hour the HBOT at least two times a day for 3 days.
- The patient must be able to perform Valsalva's - or Frenzels manoeuvre - to equalize middle ear pressure. As prophylaxis, all patients will receive detumescent nose drops as Otrivin® to facilitate ear- and sinuses equilibration. In the rare event it is still not possible for the patient to equalize pressure, a paracentesis or drainage of the tympanic membrane must be performed by the ear-nose and throat (ENT) doctor. All according to daily practice.
- The upstart of HBOT must be within the first 2 weeks of relevant antibiotic IE therapy.
- If a central venous catheter has been inserted, a chest X-ray must confirm no suspicion of pneumothorax.
- Patients must be >18-years old.
Who cannot join
- Claustrophobia that cannot be reversed by mild sedatives.
- Patients requiring mechanical ventilation.
- Undrained pneumothorax
- Pregnancy
- Unable to follow and understand simple commands
- Non-compliant
Trial locations and contacts
1 site in 1 country.
Mia Pries-Heje, MD contact
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet
Copenhagen, 2100
Mia Pries-Heje, MD
About this study
Official title: Hyperbaric Oxygen Treatment in Humans With Gram Positive Cocci Endocarditis"
Infectious endocarditis (IE) is defined as an infection anywhere on the endocardium, most often localised to the cardiac valves. It is an infection with an increasing incidence and in Denmark with 6-700 new cases annually. Approximately 45% of the patients must undergo cardiac surgery with replacement of infected cardiac valves by prosthetic valves.
Recently, the formation of biofilms infections has drawn attention with respect to the effects of hyperbaric re-oxygenation of stricken tissues as anaerobic bacterial metabolism with low levels of activity within the biofilm environment, may be responsible for the development of antimicrobial resistance. Polymorphonuclear leukocytes (PMNs) consume available oxygen in the conversion of oxygen to ROS and in the formation of reactive nitrogen species (RNS) by inducible nitric oxide (iNOS) as PMN's are activated by bacteria.
Read more
In pre-clinical context the effect of hyperbaric oxygen treatment (HBOT) in re-oxygenating biofilm related infections have been demonstrated in infected lungs with Pseudomonas aeruginosa and staphylococcus aureus endocarditis.
Adjunctive HBOT has never been offered to patients with IE. However, HBOT may be associated with reduced compliance and side effects, such as equalisation problems of ears and sinuses and confinement anxiety, and the treatment is organizational challenging. On this basis the investigators suggest an initial feasibility study as the basis for a later and larger scaled randomized controlled trial of HBOT in patients with IE.
Read the detailed description
During antibiotic treatments with the indicated antibiotics the susceptible bacteria are subjected to metabolic changes of the Krebs cycles leading to intrabacterial accumulation of toxic hydroxyl oxygen radicals. The intrabacterial toxic reactive oxygen species (ROS) can subsequently react with DNA, lipids or proteins resulting in damages of those bacterial components adding to the killing of the bacteria. A consequence is that bactericidal antibiotics have reduced activity in infectious foci with poor oxygen supply like in abscesses or in biofilm infections as in IE and/or rapid consumption of oxygen due to PMN influx. The bacterial damages may, if killing is not obtained, result in mutations and selection of antibiotic resistant mutants.
However, these discoveries also provide a possibility for improving the antibacterial effect by increasing the oxygen pressure in the infectious focus. This can be obtained by increasing oxygen tension in the tissues by treating the patients with HBOT - and have been shown in vitro and in vivo pre-clinical experiments. Exposing Pseudomonas aeruginosa biofilm models in vitro to HBOT has proved effective by significantly increasing the bactericidal effect of ciprofloxacin.
More important, in an animal (rats) model of left-sided S. aureus IE on the aortic valves, tobramycin killing effect was significantly improved by adding HBOT as adjunctive therapy. Moreover, the rats revealed a reduced inflammatory response and improved clinical scores. No side effects were recorded during that study.
In addition, the HBOT is also believed to improve the antibacterial effect of the PMNs, and thereby add to an enhanced elimination of infectious focus. This is being estimated by measurements of the respiratory burst of the PMNs, as well as their phagocytic capacity right before and right after the HBOT.
- Conditions
- Infectious Endocarditis
- Being tested
- Hyperbaric oxygen
- Medical subject headings
- Endocarditis, Subacute Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbaric oxygenDrug
The course of hyperbaric oxygen treatment comprises a total of 6 pressure exposures, distributed 2 times daily, for 3 days.
| Study group | Role | What they receive |
|---|---|---|
| HBOT | Experimental | Hyperbaric oxygen breathing at 2.4 atm.abs for 90 minutes. The course of hyperbaric oxygen treatment comprises a total of 6 pressure exposures, distributed 2 times daily, for 3 days. Receives: Drug: Hyperbaric oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in baseline characteristics with definite IE.
Standard clinical assesments of IE and paraclinical data
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2020
- Study start1 Dec 2019
- Primary completion1 Jul 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infectious EndocarditisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ole Hyldegaard
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Herlev Hospital
- Responsible party
- Sponsor-investigator, Ole Hyldegaard, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Ole Hyldegaard, MD, PHD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04691440
- Sponsor's protocol ID
- ENDOHOT TRIAL - RH
- Other IDs
- 2019-000857-29, 2019
- Acronym
- ENDOHOT
- Status last verified
- Dec 2020
- First submitted
- 18 Dec 2020
- Last updated
- 31 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperbaric Oxygen Treatment in Humans With Gram Positive Cocci Endocarditis"
- ClinicalTrials.gov ID
- NCT04691440
- Acronym / sponsor ID
- ENDOHOT / ENDOHOT TRIAL - RH
- Conditions
- Infectious Endocarditis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Ole HyldegaardUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Herlev Hospital
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 31 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infectious endocarditis (IE) is defined as an infection anywhere on the endocardium, most often localised to the cardiac valves. It is an infection with an increasing incidence and in Denmark with 6-700 new cases annually. Approximately 45% of the patients must undergo cardiac surgery with replacement of infected cardiac valves by prosthetic valves.
Recently, the formation of biofilms infections has drawn attention with respect to the effects of hyperbaric re-oxygenation of stricken tissues as anaerobic bacterial metabolism with low levels of activity within the biofilm environment, may be responsible for the development of antimicrobial resistance. Polymorphonuclear leukocytes (PMNs) consume available oxygen in the conversion of oxygen to ROS and in the formation of reactive nitrogen species (RNS) by inducible nitric oxide (iNOS) as PMN's are activated by bacteria.
In pre-clinical context the effect of hyperbaric oxygen treatment (HBOT) in re-oxygenating biofilm related infections have been demonstrated in infected lungs with Pseudomonas aeruginosa and staphylococcus aureus endocarditis.
Adjunctive HBOT has never been offered to patients with IE. However, HBOT may be associated with reduced compliance and side effects, such as equalisation problems of ears and sinuses and confinement anxiety, and the treatment is organizational challenging. On this basis the investigators suggest an initial feasibility study as the basis for a later and larger scaled randomized controlled trial of HBOT in patients with IE.
Detailed description
During antibiotic treatments with the indicated antibiotics the susceptible bacteria are subjected to metabolic changes of the Krebs cycles leading to intrabacterial accumulation of toxic hydroxyl oxygen radicals. The intrabacterial toxic reactive oxygen species (ROS) can subsequently react with DNA, lipids or proteins resulting in damages of those bacterial components adding to the killing of the bacteria. A consequence is that bactericidal antibiotics have reduced activity in infectious foci with poor oxygen supply like in abscesses or in biofilm infections as in IE and/or rapid consumption of oxygen due to PMN influx. The bacterial damages may, if killing is not obtained, result in mutations and selection of antibiotic resistant mutants.
However, these discoveries also provide a possibility for improving the antibacterial effect by increasing the oxygen pressure in the infectious focus. This can be obtained by increasing oxygen tension in the tissues by treating the patients with HBOT - and have been shown in vitro and in vivo pre-clinical experiments. Exposing Pseudomonas aeruginosa biofilm models in vitro to HBOT has proved effective by significantly increasing the bactericidal effect of ciprofloxacin.
More important, in an animal (rats) model of left-sided S. aureus IE on the aortic valves, tobramycin killing effect was significantly improved by adding HBOT as adjunctive therapy. Moreover, the rats revealed a reduced inflammatory response and improved clinical scores. No side effects were recorded during that study.
In addition, the HBOT is also believed to improve the antibacterial effect of the PMNs, and thereby add to an enhanced elimination of infectious focus. This is being estimated by measurements of the respiratory burst of the PMNs, as well as their phagocytic capacity right before and right after the HBOT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBOT | Experimental | Drug: Hyperbaric oxygenHyperbaric oxygen breathing at 2.4 atm.abs for 90 minutes. The course of hyperbaric oxygen treatment comprises a total of 6 pressure exposures, distributed 2 times daily, for 3 days. |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Left sided IE with gram positive cocci.
- IE has been diagnosed according to modified Duke Criteria.
- Patients must be stable, by means of no need for hemodynamic pressure support.
- The patient must be able to be seated for the 1.5 hour the HBOT at least two times a day for 3 days.
- The patient must be able to perform Valsalva's - or Frenzels manoeuvre - to equalize middle ear pressure. As prophylaxis, all patients will receive detumescent nose drops as Otrivin® to facilitate ear- and sinuses equilibration. In the rare event it is still not possible for the patient to equalize pressure, a paracentesis or drainage of the tympanic membrane must be performed by the ear-nose and throat (ENT) doctor. All according to daily practice.
Key exclusion criteria (6 listed)
- Claustrophobia that cannot be reversed by mild sedatives.
- Patients requiring mechanical ventilation.
- Undrained pneumothorax
- Pregnancy
- Unable to follow and understand simple commands
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbaric oxygenThe course of hyperbaric oxygen treatment comprises a total of 6 pressure exposures, distributed 2 times daily, for 3 days. | Drug | HBOT |
Primary outcome
Changes in baseline characteristics with definite IE.
Time frame: Up to 12 weeks
Standard clinical assesments of IE and paraclinical data
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mia Pries-Heje, MD contact
Ole Hyldegaard, MD, PHD principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hyperbaric oxygen in people with Infectious Endocarditis, run by Ole Hyldegaard at 1 site in Denmark.
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 8 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 31 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ole Hyldegaard, MD, PHD (+4535454092, ole.hyldegaard@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in baseline characteristics with definite IE. (time frame: Up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Dec 2020.