Effects of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function

NCT ID: NCT03781544

Last Updated: 2024-05-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2025-12-31

Brief Summary

Evaluation of the effect of different analgesic treatments (Tramadol, Paracetamol, Diclofenac) on sympathetic nerve activity, blood pressure, heart rate, heart rate, and vascular function in osteoarthritis patients and healthy subjects.

Detailed Description

Hundreds of millions of patients worldwide require pain-relieving therapy to maintain an acceptable quality of life. Pain relievers, including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, however, exert unwanted potent adverse systemic off-target effects and their use is associated with a well-documented excess of cerebrovascular and cardiovascular events. This of particular concern for the one fourth of the world's population aged over 35 years suffering from chronic pain, particularly with arthritis of whom half also present with established or at high risk of cardiovascular disease. This uncertainty around the cardiovascular safety of pain relieving drugs leaves practitioners and their patients with difficult management decisions and underscores the need to investigate potential differential cardiovascular effects of NSAIDs and opioids and to better delineate the underlying mechanisms involved. Indeed, currently available NSAIDs invariably disrupt the balance between prostacyclin and thromboxane, but may also exert multiple and opposing cardiovascular effects on endothelial factors, including nitric oxide and reactive oxygen species, the sympathetic nervous system and vascular inflammation. Intriguingly, the net effect of pain relieving drugs on vascular function and sympathetic nerve activity and its resulting deterioration of blood pressure control is increasingly recognized as a major possible determinant in explaining the cardiovascular side effects of NSAIDs. As a result of the ongoing concerns around the cardiovascular safety of NSAIDs and coxibs many patients are being withheld effective pain relieve or switched to opioids and/or paracetamol under the assumption of their yet unproven greater cardiovascular safety. The absence of evidence about the cardiovascular safety of these drugs presents a major dilemma for patients and physicians, who have been warned about the toxicity of NSAIDs.

Conditions

Osteoarthritis of Multiple Joints of Ankle or Foot; Healthy

Study Design

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

Study Groups

Diclofenac

Diclofenac (Diclofenacum natricum) A single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm).

Group Type: EXPERIMENTAL

Diclofenac

Intervention Type: DRUG

A single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm).

Paracetamol

Paracetamol (Paracetamol Sintetica):

A single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm).

Group Type: ACTIVE_COMPARATOR

Paracetamol

Intervention Type: DRUG

A single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm).

Tramadol

Tramadol (Tramadol-Mepha):

A single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm).

Group Type: EXPERIMENTAL

Tramadol

Intervention Type: DRUG

A single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm).

Interventions

Tramadol

A single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm).

Intervention Type: DRUG

Paracetamol

A single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm).

Intervention Type: DRUG

Diclofenac

A single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm).

Intervention Type: DRUG

Other Intervention Names

Tramadol-Mepha; PARACETAMOL Sintetica

Eligibility Criteria

Inclusion Criteria

1. Patients ≥ 18 years of age, male or female, with a diagnosis of osteoarthritis or healthy subjects ≥ 18 years of age;

2. Written informed consent;

Exclusion Criteria

1. History of hypersensitivity or allergy to any of the study drugs

2. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1;

3. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after Visit 1;

4. Presence of significant endocrine diseases;

5. Presence of active acute infectious diseases;

6. Known narrow-angle glaucoma;

7. Known epilepsy;

8. Cimino-shunt operation on both arms;

9. Pregnancy, intention thereof during study, lack of sufficient contraception, breastfeeding;

10. Drug or alcohol abuse;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Ruschitzka, MD

Role: STUDY_DIRECTOR

Cardiology, University Heart Center Zurich

Locations

University Heart Center Zurich

Zurich, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Isabella Sudano, MD

Role: CONTACT

Isabella.Sudano@usz.ch

+41442555841

Anne-Marieke Vegter

Role: CONTACT

Anne-Marieke.Vegter@usz.ch

+41442552280

Facility Contacts

Frank Ruschitzka, MD

Role: primary

frank.ruschitzka@usz.ch

+41442553353

Other Identifiers

OPIOVASC

Identifier Type: -

Identifier Source: org_study_id