Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02500641
• Date of registration: 07/07/2015
• Prospective Registration: Yes
• Primary sponsor: Menarini International Operations Luxembourg SA
• Public title: Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout FORWARD
• Scientific title: The Effect of Intensive Urate Lowering Therapy (ULT) With Febuxostat in Comparison With Allopurinol on Cardiovascular Risk in Patients With Gout Using Surrogate Markers: a Randomized, Controlled Trial
• Date of first enrolment: August 17, 2015
• Target sample size: 196
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02500641
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Croatia, Germany, Hungary, Italy, Netherlands, Poland, Romania, Serbia

Contacts

• Name: Claudio Borghi, Prof
• Affiliation: Policlinico S.Orsola - Malpighi Medicina Interna Borghi

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female patients 18 years and older;

2. History of gout, flare free in the 4 weeks prior to study entry

3. History of crystal (joint liquid) proven diagnosis or anamnestic diagnosis of gout
according to Wallace at el. To be eligible, a subject had to present at least 6 of the
following 12 clinical, laboratory, and x-ray phenomena:

1. Maximum inflammation developed within 1 day, 2. More than one attack of acute arthritis,
3. Monoarticular arthritis attack, 4. Redness observed over joints, 5. First
metatarsophalangeal (MTP) pain or swelling, 6. Unilateral first MTP joint attack, 7.
Unilateral tarsal joint attack, 8. Suspected or proven tophus, 9. Hyperuricemia, 10.
Asymmetric swelling within a joint on a X ray, 11. Subcortical cysts without erosions on X
ray, 12. Negative organisms on culture of joint fluid; 4. Naive to ULT or previously
treated with ULT, but with no ULT treatment in the last 1 month prior to study entry and
only if reason for ULT interruption was not due to safety concerns.

5. Patients at study entry have elevated serum urate level >8 mg/dl. 6. Overall
Cardiovascular (CV) risk based on the scoring proposed by the Joint Task Force of the
European Society of Cardiology and other European Societies on cardiovascular disease
prevention in clinical practice between 5 and 15-% (inclusive). Patients with diabetes
mellitus type 2 could be included in the study if their CV risk score is calculated as =7%.

7. Allowed concomitant medications should be maintained stable during the last 2 weeks
before randomisation

Exclusion Criteria:

1. Severe chronic renal failure (creatinine clearance < 30 ml/min)

2. Hepatic failure

3. Active liver disease or hepatic dysfunction, defined as both alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) >2 times the upper limit of normal.

4. Diabetes mellitus type1

5. Life-threatening co-morbidity or with a significant medical condition and/or
conditions that would interfere with the treatment, the safety or the compliance with
the protocol

6. Diagnosis of, or receiving treatment for malignancy (excluding basalioma skin cancer)
in the previous 5 years

7. Patients who have experienced either myocardial infarction or stroke

8. Patients with inflammatory based arthritis (e.g.: rheumatoid arthritis, etc.)

9. Patients with congestive heart failure, New York Heart Association (NYHA) Class III or
IV

10. Patients with untreated/uncontrolled thyroid function

11. Patients with clinically severe peripheral arterial disease

12. Concomitant administration of any of the following: azathioprine, mercaptopurine,
theophylline, meclofenamate, sulfinpyrazone, trimethoprim-sulfamethoxazole,
cyclophosphamide, benzbromarone, pyrazinamide, captopril and enalapril (for
Allopurinol), tegafur, pegloticase and tacrolimus.

13. Hypersensitivity to any one of the active substances or to any of the excipients

14. Any contraindication to febuxostat or allopurinol (with reference to the summary of
product characteristics).

15. Subject is unable to take either of the protocol-required gout flare prophylactic
medications (NSAID or colchicine) due to contraindications or intolerance, e.g.
hypersensitivity, active gastric ulcer disease, renal impairment and/or changes in
liver enzymes

16. Participation in another trial of an investigational drug or device within 30 days
prior to screening, or prior treatment with investigational product(s)

17. Women of childbearing potential (WOCBP), including peri-menopausal women who have had
a menstrual period within 1 year, not willing to use highly effective method of birth
control throughout the study period and for 4 weeks after study completion defined as
a method which results in a failure rate of less than 1% per year such as:

- combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, transdermal),

- progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, implantable),

- intrauterine device (IUD),

- intrauterine hormone-releasing system (IUS),

- bilateral tubal occlusion,

- vasectomised partner (provided that partner is the sole sexual partner of the
trial participant and that the vasectomised partner has received medical
assessment of the surgical success),

- sexual abstinence;

18. Severe psychiatric disorders/neurological disorders

19. Severe concurrent pathology, including terminal illness (cancer, AIDS, etc)

20. Abuse of alcohol, analgesics, or psychotropic drugs

21. Inability or unwillingness, in the investigator's opinion, to follow study procedures
including, but not limited to the ability to obtain adequate PWV/Pulse Wave Analysis
(PWA) recordings. Special attention was made to any physical abnormalities which could
affect quality of PWV/PWA measurement:

- Neck region- neck flexibility and accessibility of carotid artery,

- Upper arm and thigh region- exclude any abnormalities which would prevent
adequate placement of the cuff;

22. Inability or unwillingness to issue the informed consent



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Gout

Intervention(s)

Drug: Colchicine

Drug: Omeprazole

Drug: Allopurinol 100 up to 600mg/day

Drug: Febuxostat 80/120mg/day

Drug: Naproxen

Primary Outcome(s)

Pulse Wave Velocity [Time Frame: 36 weeks of treatment]

Secondary ID(s)

MEIN/14/FEB-PWV/001

2014-005567-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/06/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02500641