Colchicine for ischemia with no obstructive coronary artery disease and microvascular dysfunction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

20 Nov 2024 → ongoing

Decision date (initial)

2023-12-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Funding from Sygesikring DK

External identifiers

EU CT number

2023-507981-17-00

WHO UTN

U1111-1297-3446

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Safety, Pharmacokinetic, Therapy

Improved coronary flow and coronary flow reserve in patients with angina symptoms and coronary microvascular disease

Secondary objectives 3

1. Improvement of symptom burden with colchicine
2. Determine the effect of colchicine on arterial reactivity and proteomic profiles.
3. Investigating the mechanism underlying CMD through small artery analysis.

Conditions and MedDRA coding

CMD

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. • Have CMD, defined as myocardial blodflow reserve (MBFR) < 2.5 or hyperemic myocardial blood flow (hMBF) < 2.3ml/g/min
2. • No obstructive CAD as determined by the clinical assessment of [15O]H2O-PET

Exclusion criteria 24

1. • Females of childbearing potential. The female patient must either be postmenopausal for at least 1 year or surgically sterile.
2. • Male patients who are planning to impregnate their partner within the individual participation period in the trial and 6 months after last dose.
3. • Patient with a history of cirrhosis, chronic active hepatitis, or severe hepatic disease.
4. • Patient with a history of clinically significant drug or alcohol abuse in the last year.
5. • Patient is currently using or plans to begin chronic systemic steroid therapy (oral or intravenous) during the study (topical or inhaled steroids are allowed).
6. • Patient with liver disease
7. • Patient with kidney disease or kidney impairment, defined as Serum Creatinine >150mmol/l or eGFR<50mL/min
8. • Male patients, having intercourse with fertile women, not willing to use contraception.
9. • Patient with lactose intolerance
10. • Patient with a history of an allergic reaction or sensitivity to adenosine or mannitol.
11. • Patient with Atrioventricular block grade II or III, or sick sinus syndrome, not protected by a pacemaker.
12. • Patient currently taking colchicine for other indications (mainly chronic indications represented by Familial Mediterranean Fever or gout). There is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrolment.
13. • Patients with severe hypovolemia or hypotension (defined as systolic blood pressure < 90mmHg)
14. • Patients with unstable angina pectoris
15. • Patient with increased intracranial pressure.
16. • Patient with a history of an allergic reaction or significant sensitivity to colchicine.
17. • Patient in treatment with Potent CYP3A4-/P-gp-inhibitors: o Amiodaron o Amprenavir* o Atazanavir* o Clarithromycin* o Diltiazem o Erythromycin o Telithromycin o Azitromycin o Fluvoxamin o Fosamprenavir* o Indinavir* o Itraconazol* o Ketoconazol* o Lopinavir o Saquinavir o Nelfinavir o Fosamprenavir o Indinavir o Ritonavir* o Verapamil o Voriconazol* o Pyridamole o Roxithromycin o Ciclosporine o Or has a massive Grapefruit consumption
18. • Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
19. • Patient with heart failure, defined as left ventricular ejection fraction of less than 40%[44]
20. • Patient with uncontrolled hypertension (defined as blood pressure above target 140/90 for all) )
21. • Patient with inflammatory bowel disease (Crohn’s disease or ulcerative colitis) or patient with chronic diarrhea.
22. • Patient with any of the following as measured within the past 30 days, and determined to be non-transient through repeat testing: Anemia, thrombocytopenia, leucopenia, liver disease, or kidney disease defined as any of the following measurements within the last 3 months: o hemoglobin < 7mmol/L, o white blood cell count < 3.0 X 109/L, o platelet count <110 X 109/L, o ALT > 3 times the upper limit of normal, o total bilirubin > 2 times upper limit of normal o Serum Creatinine >150mmol/l or eGFR<50mL/min
23. • Patients in treatment with anticoagulants. NOACs: Eliquis, Lixiana, Pradaxa, Xarelto, or Warfarin
24. patient with severe valve disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in myocardial bloodflow reserve assessed by [15O]H2O-PET-scan from baseline and after 6 months

Secondary endpoints 5

1. Change in Symptom burden assessed by Seattle Angina Questionnaire at baseline and 6 months
2. Identifying certain protein pathways and functional mechanisms in arteries associated with colchicine treatment.
3. Changes in vascular function and protein pathway analyses in subsamples
4. Change in MBF assessed by [15O]H2O-PET-scan from baseline and after 6 months
5. Change in hMBF assessed by [15O]H2O-PET-scan from baseline and after 6 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Bispebjerg Bakke 23

City

Copenhagen Nv

Postcode

2400

Country

Denmark

Scientific contact point

Organisation

Bispebjerg Hospital

Contact name

Information deck

Public contact point

Organisation

Bispebjerg Hospital

Contact name

Information deck

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications