Anti-chlamydophila Antibiotic Combination Therapy in the Treatment of Patients With Coronary Heart Disease

NCT03618108 | Terminated Phase 2 DMC

• 1 other identifier: NC10/C01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to see whether the antibiotic combination of 100mg doxycycline, 500mg azithromycin and 300mg rifabutin is a safe and effective treatment for coronary artery disease which has not responded to 'standard treatment'. Coronary artery disease is the process of plaque build up within the walls of the arteries responsible for supplying the heart with oxygen and nutrients. plaque is usually made up of fatty deposits, minerals and various amounts of tissue and white cells which eventually narrows the artery, reducing blood flow to the heart. The resulting damage and build up of fat leads to inflammation of the arterial wall and eventually the arteries narrow. The researchers involved in this study consider that a pathogen called Chlamydophila pneumoniae, which can live inside cells may cause this inflammation of the arterial wall. The purpose of this study is to see if treatment with this antibiotic combination in patients with CHD is safe and effective in reducing disease severity measured at coronary angiography and improving quality of life. Approximately 60 patients will be involved in this trial. the treatment period is 90 days with a further 90 day follow up period.

Conditions

Coronary Heart Disease; Chlamydophila Pneumoniae Infections

Outcome Measures

Primary Outcomes (1)

• To evaluate effect of antibiotic therapy through evaluation of fractional flow reserve

  to evaluate the effect of antibiotic combination therapy on objective measures of improvement in coronary flow as determined by fractional flow reserve (FFR) in subjects undergoing percutaneous coronary intervention (PCI) with non-critical lesions in non-culprit arteries

  day 90 post initiation of treatment (Visit 3)

Secondary Outcomes (2)

• Angiographic stenoses changes

  Day 90 post initiation of treatment (Visit 3)

• Major adverse Clinical events

  day 90 (visit 3) and Day 180 post initiation of treatment

Study Arms (2)

Active

ACTIVE COMPARATOR

Subjects will be given oral capsules containing the active comparators 50mg oral capsule doxycycline, 250mg oral capsule azithromycin and 150mg oral capsule rifabutin daily (days 1 to 7). From days 8 to 90 subjects will be given 50mg oral capsule doxycycline, 250mg oral capsule azithromycin and 150mg oral capsule rifabutin twice daily.

Drug: Doxycycline Capsule; Drug: Azithromycin Capsule; Drug: Rifabutin Oral Capsule

Placebo

PLACEBO COMPARATOR

subjects will be given sugar capsules identical in form and size to the active comparators, 1 capsule of each bottle (3 separate capsules) daily (days 1 to 7), 1 capsule of each bottle (3 separate capsules) twice daily (days 8 to 90).

Drug: Placebo oral capsule; Drug: Placebo Oral Tablet

Interventions

Doxycycline Capsule DRUG

doxycycline capsule

Also known as: Vibramycin

Active

Azithromycin Capsule DRUG

azithromycin capsule

Also known as: zithromax

Active

Rifabutin Oral Capsule DRUG

rifabutin capsule

Also known as: mycobutin

Active

Placebo oral capsule DRUG

Placebo oral capsule identical in size and form to doxycycline

Placebo

Placebo Oral Tablet DRUG

Placebo oral capsule identical in size and form to azithromcyin

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females (without childbearing potential as evidenced by hysterectomy, tubal ligation or at least one year post-menopause) aged 18 to 80 years inclusive.
• Ability to provide written informed consent to participate in the study.
• Subjects with documented recent acute coronary syndrome (ACS) or evidence of myocardial ischemia.
• Subjects who have a culprit lesion suitable for PCI, and a non-critical lesion in another vessel suitable for staged PCI with an FFR of \<0.80, for subjects undergoing diagnostic angiography and FFR without ad hoc PCI.
• No serious co-morbidities, which might interfere with the subject's ability to enter the study.
• Able to communicate effectively with the study team and to comply with the protocol.

You may not qualify if:

• Females that are of child bearing potential
• Subjects without a non-culprit lesion considered appropriate to plan a staged PCI.
• Clinically significant haematologic, hepatic, metabolic, renal, rheumatologic, anaphylactic reactions, neurological or psychiatric disease.
• Clinical evidence of any other disease, which might interfere with the subject's ability to enter the trial.
• Concomitant administration of medications that may interfere with treatment as assessed by the Investigator, including allergy to any component of the therapy.
• Concomitant administration of any medication prohibited for use during this study (e.g. colchicine)
• Male subjects consuming greater than 60g alcohol per day, or female subjects consuming greater than 40g alcohol per day.
• Evidence of any recent history of, or current recreational drug abuse.
• Serious adverse reaction or hypersensitivity to therapeutic drugs.
• Unable and to comply with the study requirements.
• Subjects who have been involved in an experimental drug protocol within the past four weeks.
• If a subject becomes pregnant during the course of the study, they will be immediately withdrawn and treated in the way least likely to harm both subject and foetus.

Sponsors & Collaborators

• Cadrock Pty. Ltd.: lead
• Centre for Digestive Diseases, Australia: collaborator

Study Sites (1)

Liverpool hospital

Liverpool, New South Wales, 2170, Australia

Location

Related Publications (2)

• Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995 Aug 1;92(3):657-71. doi: 10.1161/01.cir.92.3.657. No abstract available.

  PMID: 7634481 BACKGROUND

• Hermus L, Lefrandt JD, Tio RA, Breek JC, Zeebregts CJ. Carotid plaque formation and serum biomarkers. Atherosclerosis. 2010 Nov;213(1):21-9. doi: 10.1016/j.atherosclerosis.2010.05.013. Epub 2010 May 19.

  PMID: 20627248 BACKGROUND

MeSH Terms

Conditions

Coronary Disease

Interventions

Doxycycline; Azithromycin; Rifabutin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds

Study Officials

• Thomas Borody

  Centre for Digestive Diseases

  PRINCIPAL INVESTIGATOR

• John French

  Liverpool Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical placebo capsule dosing
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 7, 2018
• Study Start: April 4, 2018
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: August 2, 2021

Record last verified: 2021-07

Locations

AU (1)