Systemic Inflammatory Response SyndromeREMEDINCT03939273
The Effects of Gut Micribiota Disruption on the Immune Response After Open Heart Surgery
A study testing Vancomycin Oral, Metronidazole Oral and Ciprofloxacin Pill in people with Systemic Inflammatory Response Syndrome and Postoperative Shock, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In this randomized, double-blind, placebo-controlled study, the investigators will assess whether preoperative disruption of the gut microbiota by a course of broad spectrum antibiotics will attenuate the postoperative systemic inflammatory response after on-pump cardiac surgery Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Systemic Inflammatory Response Syndrome, Postoperative Shock, Coronary Artery Disease
- What is being tested?
- Vancomycin Oral, Metronidazole Oral and Ciprofloxacin Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2022to Mar 2023
- Phase
- Interventional
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Scheduled for elective on-pump cardiac surgery.
- Written informed consent to participate in this trial prior to any study-mandated procedure
Who cannot join
- Use of any antibiotic or antifungal therapies within 30 days prior to surgery
- History of inflammatory bowel disease
- History of bowel resection and / or short bowel syndrome
- Pre-operative creatinine clearance < 50 ml/min
- Severe hepatic impairment
- Immune compromised
Show all 21Show fewer
- Solid organ transplantation
- Known HIV
- Pregnancy
- Use of immunosuppressive drugs
- Emergency surgery
- Haematological disorders
- Disorders from myeloid and / or lymphoid origin
- Leucopenia
- Known hypersensitivity to any of the investigational and/or non-investigational products or their excipients.
- Treatment with investigational drugs or participation in any other intervention clinical trial within 30 days prior to study drug administration
- Inability to personally provide written informed consent
- Suspected of not being able to comply with the trial protocol
- Use of vitamin K antagonists
- Use of tricyclic antidepressants
- Use of other drugs which have potential dangerous interactions with study treatment
Trial locations and contacts
1 site in 1 country.
Quirine Habes, MD contact
Netherlands1 site
Radboud University Medical Centre
Nijmegen, Gelderland, 6525 GA
Aron Jansen, MD, +31 24 36 55618, aron.jansen@radboudumc.nl
Quirine Habes, MD, quirine.habes@radboudumc.nl
About this study
Official title: Randomized Placebo-controlled Study on the Effects of Antibiotic-induced Gut MicrobiomE Disruption on the Innate Immune Response Following Cardiac Surgery
In this randomized, double-blind, placebo-controlled study, the investigators will assess whether preoperative disruption of the gut microbiota by a course of broad spectrum antibiotics will attenuate the postoperative systemic inflammatory response after on-pump cardiac surgery
Read the detailed description
During cardiac surgery, the use of cardiopulmonary bypass and extracorporeal circulation, operative trauma, and ischemia-reperfusion injury can induce a profound systemic innate immune response. This response contributes to postoperative morbidity and mortality, as increased proinflammatory cytokine levels are associated with several postoperative complications. Commensal microbiota in the gut can modulate systemic immune responses. The investigators hypothesize that reduction of systemic immune activation by disruption of the microbiome may be beneficial in patients undergoing cardiac surgery.
The objective of this trial is to assess the anti-inflammatory effects of disruption of the intestinal microbiota with broad-spectrum antibiotics in patients with systemic inflammation following cardiac surgery and to assess the effects on clinical outcomes in these patients.
To this end, subjects will be randomized into one of two treatment arms and will receive either active treatment or a placebo during the seven days prior to surgery. Active treatment consists of a seven day course of oral ciprofloxacin 500 mg twice a day, oral vancomycin 500 mg thrice per day, oral metronidazole 500 mg thrice per day and a six day course of oral fluconazole 200 mg once per day. Placebo treatment is randomly allocated in a double blind fashion in a 1:1 proportion to the active treatment. Stool samples will be obtained prior to and directly after study treatment to assess the effects on the richness and diversity of the gut microbiota. During and after surgery, plasma levels of circulating cytokines will be measured to assess the effects of microbiota disruption on the inflammatory response.
- Conditions
- Systemic Inflammatory Response Syndrome, Postoperative Shock, Coronary Artery Disease, Extracorporeal Circulation; Complications
- Being tested
- Vancomycin Oral, Metronidazole Oral, Ciprofloxacin Pill, Fluconazole Oral Product, Placebos
- Keywords
- Systemic Inflammation, Microbiome, CABG, Coronary Artery Bypass Graft, Innate Immunity, Gut microbiota
- Medical subject headings
- Systemic Inflammatory Response Syndrome, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vancomycin OralDrug
500 mg thrice per day for seven days
Metronidazole OralDrug
500 mg thrice per day for seven days
Ciprofloxacin PillDrug
500 mg twice per day for seven days
Fluconazole Oral ProductDrug
200 mg once per day for six days
PlacebosDrug
seven day course of placebo tablets and capsules identical in appearance and number to active treatment
| Study group | Role | What they receive |
|---|---|---|
| Active group | Active comparator | A preoperative seven day course of oral ciprofloxacin 500 mg twice a day, oral vancomycin 500 mg thrice per day, oral metronidazole 500 mg thrice per day and a six day course of oral fluconazole 200 mg once per day. Receives: Drug: Vancomycin Oral; Drug: Metronidazole Oral; Drug: Ciprofloxacin Pill; Drug: Fluconazole Oral Product |
| Control group | Placebo comparator | A preoperative seven day course of placebo, consisting of pills and capsules identical in appearance and number to the active group Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Between group differences in Area Under the Curve (AUC) of the time-concentration curve of interleukin (IL)-6 plasma concentrations.
Blood samples will be obtained at predefined time points during and after surgery to assess plasma levels (in pg/mL) of circulating inflammatory mediators. To assess between group differences, the AUC of the time-concentration curve (expressed in arbitrary units) of each inflammatory mediator will be calculated.
Measured: During surgery and up to 24 hours after surgery
Secondary outcomes (1)
Between group differences in AUC of the time-concentration curve of other inflammatory mediators.
Tumor Necrosis Factor (TNF)-α, IL-8, IL-10, IL-1β, IL-1RA, Monocyte Chemoattractant Protein (MCP)-1, Macrophage Inflammatory Protein (MIP)-1α MIP-1β, Vascular Cell Adhesion Molecule (VCAM), Intercellular Adhesion Molecule (ICAM)
Measured: During surgery and up to 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study startMar 2022 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionMar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized double-blind placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Pickkers, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03939273
- Sponsor's protocol ID
- The REMEDI trial
- Other IDs
- 2019-000964-54, 2019
- Acronym
- REMEDI
- Status last verified
- Mar 2021
- First submitted
- 4 Apr 2019
- Last updated
- 12 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo-controlled Study on the Effects of Antibiotic-induced Gut MicrobiomE Disruption on the Innate Immune Response Following Cardiac Surgery
- ClinicalTrials.gov ID
- NCT03939273
- Acronym / sponsor ID
- REMEDI / The REMEDI trial
- Conditions
- Systemic Inflammatory Response Syndrome, Postoperative Shock, Coronary Artery Disease, Extracorporeal Circulation; Complications
- Keywords
- Systemic Inflammation, Microbiome, CABG, Coronary Artery Bypass Graft, Innate Immunity, Gut microbiota
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2022 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 6 May 2019 (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.
In this randomized, double-blind, placebo-controlled study, the investigators will assess whether preoperative disruption of the gut microbiota by a course of broad spectrum antibiotics will attenuate the postoperative systemic inflammatory response after on-pump cardiac surgery
Detailed description
During cardiac surgery, the use of cardiopulmonary bypass and extracorporeal circulation, operative trauma, and ischemia-reperfusion injury can induce a profound systemic innate immune response. This response contributes to postoperative morbidity and mortality, as increased proinflammatory cytokine levels are associated with several postoperative complications. Commensal microbiota in the gut can modulate systemic immune responses. The investigators hypothesize that reduction of systemic immune activation by disruption of the microbiome may be beneficial in patients undergoing cardiac surgery.
The objective of this trial is to assess the anti-inflammatory effects of disruption of the intestinal microbiota with broad-spectrum antibiotics in patients with systemic inflammation following cardiac surgery and to assess the effects on clinical outcomes in these patients.
To this end, subjects will be randomized into one of two treatment arms and will receive either active treatment or a placebo during the seven days prior to surgery. Active treatment consists of a seven day course of oral ciprofloxacin 500 mg twice a day, oral vancomycin 500 mg thrice per day, oral metronidazole 500 mg thrice per day and a six day course of oral fluconazole 200 mg once per day. Placebo treatment is randomly allocated in a double blind fashion in a 1:1 proportion to the active treatment. Stool samples will be obtained prior to and directly after study treatment to assess the effects on the richness and diversity of the gut microbiota. During and after surgery, plasma levels of circulating cytokines will be measured to assess the effects of microbiota disruption on the inflammatory response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized double-blind placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Active group | Active comparator | Drug: Vancomycin Oral, Drug: Metronidazole Oral, Drug: Ciprofloxacin Pill, Drug: Fluconazole Oral ProductA preoperative seven day course of oral ciprofloxacin 500 mg twice a day, oral vancomycin 500 mg thrice per day, oral metronidazole 500 mg thrice per day and a six day course of oral fluconazole 200 mg once per day. |
| Control group | Placebo comparator | Drug: PlacebosA preoperative seven day course of placebo, consisting of pills and capsules identical in appearance and number to the active group |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 18 years
- Scheduled for elective on-pump cardiac surgery.
- Written informed consent to participate in this trial prior to any study-mandated procedure
Key exclusion criteria (21 listed)
- Use of any antibiotic or antifungal therapies within 30 days prior to surgery
- History of inflammatory bowel disease
- History of bowel resection and / or short bowel syndrome
- Pre-operative creatinine clearance < 50 ml/min
- Severe hepatic impairment
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 |
|---|---|---|
| Vancomycin Oral500 mg thrice per day for seven days | Drug | Active group |
| Metronidazole Oral500 mg thrice per day for seven days | Drug | Active group |
| Ciprofloxacin Pill500 mg twice per day for seven days | Drug | Active group |
| Fluconazole Oral Product200 mg once per day for six days | Drug | Active group |
| Placebosseven day course of placebo tablets and capsules identical in appearance and number to active treatment | Drug | Control group |
Primary outcome
Between group differences in Area Under the Curve (AUC) of the time-concentration curve of interleukin (IL)-6 plasma concentrations.
Time frame: During surgery and up to 24 hours after surgery
Blood samples will be obtained at predefined time points during and after surgery to assess plasma levels (in pg/mL) of circulating inflammatory mediators. To assess between group differences, the AUC of the time-concentration curve (expressed in arbitrary units) of each inflammatory mediator will be calculated.
1 secondary outcome
Between group differences in AUC of the time-concentration curve of other inflammatory mediators.
Time frame: During surgery and up to 24 hours after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2021.
- Individual participant dataSharing planned: Undecided
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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.
Quirine Habes, MD contact
Peter Pickkers, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vancomycin Oral, Metronidazole Oral and Ciprofloxacin Pill in people with Systemic Inflammatory Response Syndrome and Postoperative Shock, run by Radboud University Medical Center at 1 site in Netherlands.
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 3 inclusion and 21 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 12 Mar 2021. 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 Netherlands. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Aron Jansen, MD (+31 24 36 55618, aron.jansen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Between group differences in Area Under the Curve (AUC) of the time-concentration curve of interleukin (IL)-6 plasma concentrations. (time frame: During surgery and up to 24 hours after surgery). 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 12 Mar 2021.