Serum Creatinine Change / Renal Adverse Effect With Use of Non-steroidal Painkillers in Axial Spondyloarthritis Patients

Effect of Continuous Administration of Different Therapeutic Dosages of Indomethacin and Etoricoxib in the Management of Axial Spondyloarthritis: A Randomized Controlled Trial

2 Non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin and etoricoxib were prescribed sequentially in Axial Spondyloarthritis patients according to the internationally accepted guidelines to determine serum creatinine change with NSAIDs use.

Study Overview

• Status: Completed
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Drug: Indomethacin SR, 75 Mg Oral Capsule, Extended Release; Drug: Indomethacin 25 Mg Oral Capsule; Drug: Etoricoxib 90 mg; Drug: Etoricoxib 60 mg

Detailed Description

The study had 2 phases. In phase 1, Patients of axial Spondyloarthritis were randomized into 2 groups; group A and group B. they were put on indomethacin 150 mg/day and indomethacin 100 mg/day respectively and were followed up at 3rd week. Those who had normal serum creatinine and responded with the drug were followed up to 24th week. Those who did not respond were excluded from phase 1 and were enrolled in phase 2. Non-responders of indomethacin 150mg and indomethacin 100 mg were put on etoricoxib 90 mg and etoricoxib 60 mg respectively. Again followed up to 24th week.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• SpA (axial) patients according to Assessment of Spondyloarthritis International Society (ASAS) criteria with BASDAI > 4

Exclusion Criteria:

• Inadequate response to therapeutic dose of indomethacin or etoricoxib, taken for at least 2 weeks continuously
• Abnormal serum creatinine : serum creatinine >1.3 mg/dl
• Abnormal SGPT: SGPT > 40 U/L
• Hypertension: Systolic blood pressure > 140 mm Hg and/ or diastolic blood pressure >90 mm Hg or on anti-hypertensive drug
• Dyspepsia or active peptic ulcer disease : upper abdominal discomfort or upper abdominal pain related with food or peptic ulcer disease diagnosed by upper gastrointestinal endoscopy
• Diabetes mellitus: abnormal random plasma glucose or diagnosed case of diabetes mellitus
• Ischemic heart disease: history of angina or ECG changes suggestive of ischemic heart disease
• Active congestive heart failure: pedal edema with tender hepatomegaly with raised JVP or diastolic dysfunction on echocardiography
• Asthma: diagnosed case of asthma or rhonchi on chest auscultation
• Bleeding problems: having a history of prolonged bleeding
• Pregnancy: missed period followed by positive pregnancy test
• Simultaneous use with certain medications such as warfarin, phenytoin, cyclosporine, probenecid, lithium, digoxin, ACE inhibitor, thiazide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A in phase 1; Indomethacin 75 mg, extended release capsule twice daily	Drug: Indomethacin SR, 75 Mg Oral Capsule, Extended Release; Indomethacin SR, 75 Mg Oral Capsule, Extended Release orally twice daily; Other Names: indomethacin
ACTIVE_COMPARATOR: Group B in phase 1; Indomethacin 25 mg capsule, 2 capsule twice daily	Drug: Indomethacin 25 Mg Oral Capsule; Indomethacin 25 Mg Oral Capsule, 2 capsule orally twice daily; Other Names: indomethacin
ACTIVE_COMPARATOR: Group A in phase 2; Etoricoxib 90 mg once daily	Drug: Etoricoxib 90 mg; Etoricoxib 90 mg once daily orally; Other Names: Etoricoxib
ACTIVE_COMPARATOR: Group B in phase 2; Etoricoxib 60 mg once daily	Drug: Etoricoxib 60 mg; Etoricoxib 60 mg once daily orally; Other Names: Etoricoxib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine change	change in serum creatinine >25% from baseline with use of indomethacin and etoricoxib in Axial Spondyloarthritis patients	3rd week and 24th week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bath Ankyiosing Spodylitis Disease Activity Index (BASDAI)	<4 responded to treatment, 4 or more means not responded to treatment	3rd week and 24th week
Ankylosing Spondylitis Disease Activity Score (ASDAS)	ASDAS: <1.3 between "inactive disease" and "moderate disease activity", <2.1 between "moderate disease activity" and "high disease activity", and >3.5 between "high disease activity" and "very high disease activity"	3rd week and 24th week

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Investigators: Principal Investigator: Khandker Mahbub-Uz-Zaman, MD, Resident

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2016
• Primary Completion (ACTUAL): June 23, 2016
• Study Completion (ACTUAL): June 23, 2016

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (ACTUAL): July 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 11, 2018
• Last Update Submitted That Met QC Criteria: July 9, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Spondylitis; Spondylarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Cyclooxygenase 2 Inhibitors; Gout Suppressants; Tocolytic Agents; Indomethacin; Etoricoxib
• Other Study ID Numbers: 2015/5965

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No