Clinical trial NCT06021990: Clopidogrel for the Prevention of Exacerbations in Severe COPD
Official title: Role of Clopidogrel in Preventing Exacerbations in Patients With Severe COPD: An Open-label Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: COPD
COPD Exacerbation Acute
Keywords: COPD
Acute exacerbation
Clopidogrel
Randomised Clinical Trial
prevention
CLOPEX
Chronic Obstructive Pulmonary Disease
Lead sponsor: Lady Reading Hospital, Pakistan
Sponsor class: OTHER_GOV
Collaborators: name: Pakistan Chest Society, Pakistan
First posted: 2023-09-01
Enrollment: 162
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After assessing eligibility and consent patients will be randomly assigned to either the intervention arm or control arm. The control arm would be standard of care treatment according to GOLD guidelines and approved by the Pakistan Chest Society. The intervention arm will take Clopidogrel 75mg dail according the study prototcol
Primary purpose: TREATMENT

Brief summary: Chronic Obstructive Pulmonary Disease (COPD) is a debilitating respiratory disorder characterized by gradual and progressive airflow limitation. It has been hypothesized that clopidogrel may have a role in reducing the exacerbation of COPD by reducing thromboembolic events. Several observational studies have found that taking clopidogrel reduces the likelihood of COPD exacerbations in patients with the disease. The study being conducted will be a randomized control trial, from March 2023 to March 2024 in the department of pulmonology, LRH. The aim of the study is to determine the role of clopidogrel in reducing the frequency of exacerbation in COPD patients compared to controls. The sampling will be done by non-probability consecutive sampling and the patients will be randomly allocated in study and control groups. Both the groups will be followed at the 3rd, 6th, and 12th months of the treatment and will be compared for the outcomes.

Detailed description: Chronic Obstructive Pulmonary Disease (COPD) is a debilitating respiratory disorder characterized by gradual and progressive airflow limitation. It is a huge worldwide health issue as well as a major cause of morbidity and mortality. Currently, it is the third leading cause of death. Exacerbations, or abrupt worsening of symptoms that necessitate medical treatment, are common in people with severe COPD. Exacerbations negatively influence patients' quality of life and are linked to higher healthcare utilization and mortality.

Clopidogrel is a widely used antiplatelet medication that works by inhibiting platelet aggregation by blocking the P2Y12 receptor. Clopidogrel's potential benefits in the treatment of COPD have piqued the curiosity of researchers in recent years. According to the hypothesis, Clopidogrel may lower the incidence of exacerbations by reducing thromboembolic events, which are prevalent causes of exacerbations in COPD.

Several observational studies have found that taking clopidogrel reduces the likelihood of COPD exacerbations in patients with the disease. A meta-analysis on the reduction of all-cause mortality in COPD patients concluded that mortality might be significantly lower in COPD patients receiving antiplatelet treatment. However, because of confounding considerations, the findings of these observational studies should be regarded with caution. To confirm the potential benefits of clopidogrel in lowering COPD exacerbations, randomized controlled studies (RCTs) are required. Only a few RCTs have been undertaken to date, with inconsistent outcomes.

The inconsistent findings of the RCTs show the need for additional studies to determine the role of clopidogrel in reducing COPD exacerbations. Larger, well-designed RCTs are required to offer more firm information on the possible benefits and dangers of clopidogrel in this patient population. The RCTs should also consider clopidogrel's potential side effects, such as bleeding, which may be especially concerning in COPD patients who are frequently on numerous drugs and may have comorbidities such as cardiovascular disease.

Finally, the role of clopidogrel in lowering exacerbations in patients with severe COPD remains unknown. Observational studies suggest that clopidogrel may have some benefits, while RCT results are mixed. More research is needed to determine clopidogrel's safety and efficacy in this patient population.

The results of the study if successful, will have two impacts. First, it will help reduce the financial burden on our healthcare system. Second, it will improve patients' quality of life by less frequent hospital visits with lowered mortality.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with severe COPD (GOLD stage III or IV based on FEV1)
* Patients with a history of at least one exacerbation in the past year.
* Patients who are able to understand and provide informed consent.
* Patients willing and able to comply with the study protocol and attend follow-up visits.
* Patients who are between the ages of 40 and 80 years.
* Either gender

Exclusion Criteria:

* Patients who have previously experienced serious medical issues, like a recent heart attack or stroke (within six months),
* Patients who are known to be hypersensitive to clopidogrel.
* People who have a history of gastrointestinal bleeding or any other health issue that could make them more likely to bleed.
* Women who are pregnant or nursing.
* Patients who are being treated with additional antiplatelet or anticoagulant medications.
* Patients who are being treated with clopidogrel for any other indication.
* People who suffer from severe renal or liver illness.

Primary outcomes:
measure: Number of acute exacerbations of COPD
timeFrame: 28 days
Secondary outcomes:
measure: The number of hospitalisations for COPD-related exacerbations
timeFrame: 28 days
measure: Change in forced expiratory volume in one second (FEV1)
timeFrame: 28 days
measure: Death
timeFrame: 12 months
measure: Quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ)
timeFrame: 28 days
Other outcomes:
Locations:
city: Peshawar
country: Pakistan
facility: Pulmonology Department, Lady Reading Hospital, Peshawar
state: Khyber Pakhtunkhwa
city: Swāt
country: Pakistan
facility: Saidu Teaching Hospital, Swat
state: Khyber Pakhtunkhwa
Study officials:
affiliation: Lady Reading Hospital, Pakistan
name: Zafar Iqbal, MBBS, MCPS, FCPS, DHPE
role: STUDY_CHAIR
References:
citation: Pahal P, Hashmi MF, Sharma S. Chronic Obstructive Pulmonary Disease Compensatory Measures. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK525962/
citation: Murarescu ED, Mitrofan EC, Mihailovici MS. Chronic obstructive pulmonary disease in a new concept. Rom J Morphol Embryol. 2007;48(3):207-14.
citation: Kim V, Aaron SD. What is a COPD exacerbation? Current definitions, pitfalls, challenges and opportunities for improvement. Eur Respir J. 2018 Nov 15;52(5):1801261. doi: 10.1183/13993003.01261-2018. Print 2018 Nov.
citation: Beekman E, Mesters I, Hendriks EJ, Muris JW, Wesseling G, Evers SM, Asijee GM, Fastenau A, Hoffenkamp HN, Gosselink R, van Schayck OC, de Bie RA. Exacerbations in patients with chronic obstructive pulmonary disease receiving physical therapy: a cohort-nested randomised controlled trial. BMC Pulm Med. 2014 Apr 26;14:71. doi: 10.1186/1471-2466-14-71.
citation: Damman P, Woudstra P, Kuijt WJ, de Winter RJ, James SK. P2Y12 platelet inhibition in clinical practice. J Thromb Thrombolysis. 2012 Feb;33(2):143-53. doi: 10.1007/s11239-011-0667-5.
citation: Kunadian V, Chan D, Ali H, Wilkinson N, Howe N, McColl E, Thornton J, von Wilamowitz-Moellendorff A, Holstein EM, Burns G, Fisher A, Stocken D, De Soyza A; APPLE COPD-ICON2 Trial Investigators. Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: protocol of a randomised controlled proof-of-concept trial (APPLE COPD-ICON 2). BMJ Open. 2018 May 26;8(5):e020713. doi: 10.1136/bmjopen-2017-020713.
citation: Pavasini R, Biscaglia S, d'Ascenzo F, Del Franco A, Contoli M, Zaraket F, Guerra F, Ferrari R, Campo G. Antiplatelet Treatment Reduces All-Cause Mortality in COPD Patients: A Systematic Review and Meta-Analysis. COPD. 2016 Aug;13(4):509-14. doi: 10.3109/15412555.2015.1099620. Epub 2015 Dec 17.