Clinical Study Evaluating the Gastroprotective Effect of Carvedilol in Patients With Ischemic Heart Disease on Aspirin Therapy

NCT ID: NCT05553717

Last Updated: 2022-09-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-31
• Study Completion Date: 2023-10-31

Brief Summary

The aim of this study is to investigate the possible efficacy of Carvedilol as gastroprotective agent against aspirin-induced upper gastro-intestinal complications in patients with ischemic heart disease (IHD).

Detailed Description

Gastric ulcer is a common gastrointestinal tract (GIT) disorder that affects about 4 million of the world's population annually, with incidence of complications in approximately 10%-20%. Gastric ulcer impacts negatively on the health-related quality of life of the affected individuals (1). It is characterized by GIT bleeding, perforation, and erosion of the mucosa wall due to imbalance between aggressive factors (acid, pepsin, and Helicobacter pylori) and defensive factors (mucin, prostaglandins (PG), bicarbonate, nitric oxide (NO), mucosal blood flow, and growth factors) (2). Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both (3). Aspirin or acetylsalicylic acid that has been used as analgesic, antipyretic and antiinflammatory agent against multiple types of inflammation and in the prevention of cardiovascular thrombotic diseases as myocardial infarction (4). Despite its therapeutic benefits, the use of aspirin is a major problem secondary to the associated risk for gastric ulcer (5). Low doses of aspirin were reported to be associated with gastric and duodenal ulcers (6-12). The pathogenesis of aspirin-induced gastric ulceration includes that, the aspirin inhibits the activities of the cyclooxygenase (COX) leading to decrease in prostaglandin (PG) with subsequent reduction in mucus and bicarbonate secretion, decreasing mucosal blood flow, impairment of platelet aggregation, alteration of microvascular structures leading to epithelia damage, increased leukocyte adherence and increased production of inflammatory mediators, reactive oxygen species (ROS) and decreased antioxidant enzymes (13). Enteric-coated aspirin has less gastrointestinal toxicity, but as compared to uncoated formulations, its plasma peak level after oral intake seems slower than traditional formulation (3 to 4 hours vs 15 to 20 minutes). In addition, enteric-coated aspirin is also associated with reduced bioavailability (14). Carvedilol is an antihypertensive agent that is commonly used in the treatment of arterial hypertension, heart failure, and angina pectoris based on its combined β- and α1- blocking activities. its therapeutic benefit also includes its antioxidant and antiperoxidative properties. It has been also shown that, carvedilol acts as a metal scavenger and can protect mitochondria against oxidative damage (15). Furthermore, carvedilol showed anti-oxidative and anti-inflammatory activities against renal, hepato, and cardiotoxicity. Additionally, it is hypothesized that carvedilol has protective effects against aspirin-induced gastric ulcer or gastrointestinal toxicity (16). Very few studies are present regarding the protective effects of Carvedilol on aspirin-induced gastric ulcer. A recent study revealed that, Carvedilol use was associated with an improvement in histopathological pictures of gastric ulcers in animals' model of cold stress ulcer (17).

The previously mentioned findings highlight the need for further studies to evaluate the role of carvedilol as gastroprotective in patient on aspirin therapy.

Conditions

IHD; Gastro-Intestinal Disorder; Aspirin Induced Esophageal Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

group 1

33 patients who will receive aspirin 150mg + carvedilol 12.5mg twice daily plus other traditional therapy of ischemia for three months.

Group Type: ACTIVE_COMPARATOR

Carvedilol

Intervention Type: DRUG

Carvedilol 12.5mg\\12hr

group 2 control

33 patients who will receive aspirin 150mg + Captopril 12.5mg twice daily plus other traditional therapy of ischemia for three months.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Carvedilol

Carvedilol 12.5mg\\12hr

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 25-60 years.

2. Both genders.

3. Patient with IHD including myocardial infarction, unstable angina and chronic stable angina on aspirin therapy.

4. Patients with hypertension.

5. Patients on low dose aspirin therapy for at least 3 months.

Exclusion Criteria

1. Subjects with history of gastrointestinal disease, gastroduodenal surgery, H. pylori infection.

2. History or current diagnosis of major depressive disorder or other psychiatric disorders.

3. Patients already under histamine-2 receptor antagonist, proton pump inhibitor, misoprostol or gastrofate within 2 weeks of entering this study.

4. Patients who are allergic to aspirin and NSAIDs, who have an intolerance to aspirin and NSAIDs.

5. Subjects with a previous or current history of Zollinger-Ellison syndrome, or other gastric acid hypersecretion disorders.

6. Pregnancy or lactation.

7. Patients with severe hepatic impairment (Child-Pugh class B and C) or total bilirubin level ≥ 1.2 mg/dl.

8. Patients with renal impairment (creatinine clearance less than 50mg/dl).

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Sarah Mohamed Elkablawy

Clinical pharmacy master candidate

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

Kavitt RT, Lipowska AM, Anyane-Yeboa A, Gralnek IM. Diagnosis and Treatment of Peptic Ulcer Disease. Am J Med. 2019 Apr;132(4):447-456. doi: 10.1016/j.amjmed.2018.12.009. Epub 2019 Jan 3.

Reference Type: BACKGROUND

PMID: 30611829 (View on PubMed)

Patrono C, Baigent C. Role of aspirin in primary prevention of cardiovascular disease. Nat Rev Cardiol. 2019 Nov;16(11):675-686. doi: 10.1038/s41569-019-0225-y. Epub 2019 Jun 26.

Reference Type: BACKGROUND

PMID: 31243390 (View on PubMed)

Cadavid AP. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications. Front Immunol. 2017 Mar 15;8:261. doi: 10.3389/fimmu.2017.00261. eCollection 2017.

Reference Type: BACKGROUND

PMID: 28360907 (View on PubMed)

Chitapanarux T, Lertprasertsuke N, Kongnak A. Teprenone for the prevention of low-dose aspirin-induced gastric mucosal injury in Helicobacter pylori-negative patients. Scand J Gastroenterol. 2019 Oct;54(10):1199-1204. doi: 10.1080/00365521.2019.1672781. Epub 2019 Oct 8.

Reference Type: BACKGROUND

PMID: 31591940 (View on PubMed)

Valkhoff VE, Sturkenboom MC, Hill C, Veldhuyzen van Zanten S, Kuipers EJ. Low-dose acetylsalicylic acid use and the risk of upper gastrointestinal bleeding: a meta-analysis of randomized clinical trials and observational studies. Can J Gastroenterol. 2013 Mar;27(3):159-67. doi: 10.1155/2013/596015.

Reference Type: BACKGROUND

PMID: 23516680 (View on PubMed)

Osman AS, Labib DA, Kamel MM. Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation. Int Immunopharmacol. 2017 Sep;50:243-250. doi: 10.1016/j.intimp.2017.07.004. Epub 2017 Jul 12.

Reference Type: BACKGROUND

PMID: 28711030 (View on PubMed)

Ahmed I, Elkablawy MA, El-Agamy DS, Bazarbay AA, Ahmed N. Carvedilol safeguards against aspirin-induced gastric damage in rats. Hum Exp Toxicol. 2020 Sep;39(9):1257-1267. doi: 10.1177/0960327120918306. Epub 2020 Apr 15.

Reference Type: BACKGROUND

PMID: 32295429 (View on PubMed)

Koloski NA, Jones M, Hammer J, von Wulffen M, Shah A, Hoelz H, Kutyla M, Burger D, Martin N, Gurusamy SR, Talley NJ, Holtmann G. The Validity of a New Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) for Evaluating Symptoms in the Clinical Setting. Dig Dis Sci. 2017 Aug;62(8):1913-1922. doi: 10.1007/s10620-017-4599-6. Epub 2017 May 27.

Reference Type: BACKGROUND

PMID: 28551709 (View on PubMed)

Gierlaszynska K, Pudlo R, Jaworska I, Byrczek-Godula K, Gasior M. Tools for assessing quality of life in cardiology and cardiac surgery. Kardiochir Torakochirurgia Pol. 2016 Mar;13(1):78-82. doi: 10.5114/kitp.2016.58974. Epub 2016 Mar 30.

Reference Type: BACKGROUND

PMID: 27212988 (View on PubMed)

Elkablawy SM, Shaban AE, Mostafa TM. Clinical study evaluating the gastroprotective effect of carvedilol in patients with ischemic heart disease on aspirin therapy. Inflammopharmacology. 2025 Sep 30. doi: 10.1007/s10787-025-01961-1. Online ahead of print.

Reference Type: DERIVED

PMID: 41028410 (View on PubMed)

Other Identifiers

carvedilol as Gastroprotective

Identifier Type: -

Identifier Source: org_study_id