Effect of Molsidomine on the Endothelial (Internal Layer of Blood Vessels) Dysfunction in Patients With Angina Pectoris

NCT01363661 | Completed Phase 4 Results DMC

• 2 other identifiers: MEDCOR 20112011-000190-31
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

Molsidomine used as an add-on treatment on standard care therapy should be superior to placebo used also as an add-on treatment on standard care therapy on improving the endothelial function (endothelium score measured by reactive hyperemia - peripheral arterial tonometry \[RH-PAT\]) after 12 months of treatment in patients with stable angina patients and undergoing elective percutaneous coronary intervention. The study will be double-blind, parallel-group, randomised, multicentre, sequential, placebo-controlled study. The device used to determine RH-PAT will be EndoPAT. Duration of the treatment = one year.

Conditions

Stable Angina Pectoris; Atherosclerosis

Keywords

angina pectoris; atherosclerosis; endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• Change Versus Baseline in the Score of the EndoPAT in the Two Groups After One Year of Treatment (Month 12).

  The results are expressed mean relative change (%) between month 12 and baseline. A positive result means improvement in the score of the EndoPAT between baseline and month 12. It could be considered as a surrogate of a decrease of the endothelial dysfunction. A negative percentage means the inverse. The are no fixed limits to the scale. The minimum observed was -275% and the maximum observed was +4200%.

  12 months

Secondary Outcomes (5)

• Change Versus Baseline in the Score of the EndoPAT in the Two Groups After Six Months of Treatment (Month 6).

  Month 6

• Change Versus Baseline in the Augmentation Index in the Two Groups After Six and Twelve Months of Treatment (Months 6 and 12).

  Month 6 and Month 12

• Change Versus Baseline in Some Specific Endothelial Biomarkers After Twelve Months of Treatment (Month 12).

  Month 12

• Frequency of Serious Cardiovascular Events (SCEs) in the Two Groups After Twelve Months of Treatment (Month 12).

  Month 12

• Frequency of AEs and SAEs in the Two Groups After Twelve Months of Treatment (Month 12).

  Month 12

Study Arms (2)

Molsidomine

EXPERIMENTAL

Coruno (molsidomine 16 mg tablet; per os; once daily)

Drug: Coruno

Placebo

PLACEBO COMPARATOR

Placebo (16 mg tablet; once a day)

Drug: Placebo

Interventions

Coruno DRUG

Molsidomine 16 mg tablet, per os, once a day

Also known as: Molsidomine

Molsidomine

Placebo DRUG

Placebo (16 mg tablet, per os; once-daily)

Placebo

Eligibility Criteria

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

You may qualify if:

• Aged at least 18 years.
• No treatment with molsidomine and/or long-acting nitrates (oral or patches) for more than 48 hours during the month preceding percutaneous coronary intervention (PCI) and no treatment with these same drugs within 3 days before PCI.
• Patients who the investigator believes that they and/or their Legally Acceptable Representative (LAR) can and will comply with the requirements of the protocol.
• Written informed consent from the patient or from the LAR.
• Patients who underwent PCI for stable angina pectoris one month prior to the start of the study.
• Patients presenting endothelial dysfunction at Month 0 (score of the Endo-PAT \<0.40).

You may not qualify if:

• Pre-menopausal women.
• Patient with a clinically-active malignancy.
• Known major renal insufficiency or known significant hepatic insufficiency.
• History of psychological disorder, mental dysfunction, alcohol or drug abuse or any other factor which might interfere with the ability to cooperate in the study.
• Participation in another clinical trial which has not yet reached its primary endpoint or with the same primary endpoint during the previous month.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject will be exposed to an investigational or a non-investigational product (vaccine, drug or device).
• Hypersensitivity to molsidomine or to one of its excipients.
• Peri-procedural infarction: creatine kinase-muscle/brain (CK-MB) \>3 times the upper reference limit.
• Clinically significant abnormal pre-PCI CK-MB and troponin: any elevation above the upper reference limit.
• Intolerance to galactose, deficiency in Lapp lactase or glucose-galactose malabsorption.
• Left ventricular insufficiency (New York Heart Association \[NYHA\] class III or IV) with an ejection fraction \<35%.
• Acute circulatory insufficiency (e.g. cardiogenic shock).
• Hypotension: systolic blood pressure \<100 mmHg and/or diastolic blood pressure \<70 mmHg.
• Atrial fibrillation
• Acute myocardial infarction during the preceding month.

Sponsors & Collaborators

• Therabel Pharma SA/NV: lead

Study Sites (1)

Onze Lieve Vrouw Ziekenhuis

Aalst, 9300, Belgium

Location

Related Publications (2)

• Barbato E, Herman A, Benit E, Janssens L, Lalmand J, Hoffer E, Chenu P, Guedes A, Missault L, Pirenne B, Cardinal F, Vercauteren S, Wijns W. Double-blind parallel placebo-controlled study to evaluate the effect of molsidomine on the endothelial dysfunction in patients with stable angina pectoris undergoing percutaneous coronary intervention: the MEDCOR Trial. J Cardiovasc Transl Res. 2014 Mar;7(2):226-31. doi: 10.1007/s12265-013-9513-9. Epub 2013 Oct 19.

  PMID: 24142804 BACKGROUND

• Barbato E, Herman A, Benit E, Janssens L, Lalmand J, Hoffer E, Chenu P, Guedes A, Missault L, Pirenne B, Cardinal F, Vercauteren S, Wijns W. Long-term effect of molsidomine, a direct nitric oxide donor, as an add-on treatment, on endothelial dysfunction in patients with stable angina pectoris undergoing percutaneous coronary intervention: results of the MEDCOR trial. Atherosclerosis. 2015 Jun;240(2):351-4. doi: 10.1016/j.atherosclerosis.2015.03.045. Epub 2015 Apr 7.

  PMID: 25875387 DERIVED

MeSH Terms

Conditions

Angina, Stable; Atherosclerosis; Angina Pectoris

Interventions

Molsidomine

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Sydnones; Oxadiazoles; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines

Limitations and Caveats

Too limited sample size. Huge variability in all measurements. High drop-out rate. Add-on treatment was a challenge to demonstrate a difference between Coruno and placebo.

Results Point of Contact

• Title: Jacques Bruhwyler, Project Manager
• Organization: ECSOR

Jacques.Bruhwyler@ecsor.com

3267444093

Study Officials

• Emanuele Barbato, MD

  Cardiology Center, Onze Lieve Vrouw Ziekenhuis Aalst

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2011
• First Posted: June 1, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 6, 2014
• Results First Posted: September 26, 2014

Record last verified: 2014-09

Locations

BE (1)