GoutPhase 4FORWARDNCT02500641
Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout
A Phase 4 study testing Febuxostat 80/120mg/day, Allopurinol 100 up to 600mg/day and Colchicine in people with Gout, run by Menarini International Operations Luxembourg SA at 26 sites in 6 countries.
Trial summary
There is a mounting and clear association between hyperuricaemia, gout and the presence of traditional cardiovascular (CV) risk factors and CV event-equivalent conditions such as chronic kidney disease, metabolic syndrome, and diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gout
- What is being tested?
- Febuxostat 80/120mg/day, Allopurinol 100 up to 600mg/day and Colchicine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 196 participants
- Where
- 26 sitesin 6 countries
- Study dates
- 17 Aug 2015to 10 May 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients 18 years and older;
- History of gout, flare free in the 4 weeks prior to study entry
- 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
Who cannot join
- Severe chronic renal failure (creatinine clearance < 30 ml/min)
- Hepatic failure
- Active liver disease or hepatic dysfunction, defined as both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 times the upper limit of normal.
- Diabetes mellitus type1
- 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
- Diagnosis of, or receiving treatment for malignancy (excluding basalioma skin cancer) in the previous 5 years
Show all 31Show fewer
- Patients who have experienced either myocardial infarction or stroke
- Patients with inflammatory based arthritis (e.g.: rheumatoid arthritis, etc.)
- Patients with congestive heart failure, New York Heart Association (NYHA) Class III or IV
- Patients with untreated/uncontrolled thyroid function
- Patients with clinically severe peripheral arterial disease
- 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.
- Hypersensitivity to any one of the active substances or to any of the excipients
- Any contraindication to febuxostat or allopurinol (with reference to the summary of product characteristics).
- 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
- Participation in another trial of an investigational drug or device within 30 days prior to screening, or prior treatment with investigational product(s)
- 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;
- Severe psychiatric disorders/neurological disorders
- Severe concurrent pathology, including terminal illness (cancer, AIDS, etc)
- Abuse of alcohol, analgesics, or psychotropic drugs
- 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;
- Inability or unwillingness to issue the informed consent
Trial locations and contacts
26 sites in 6 countries.
26 sites in 6 countries
Poland10 sites
Gdańskie Centrum Zdrowia Sp.z o.o.
Gdansk
Specjalistyczna Praktyka Lekarska Piotr Kubalski
Grudziądz
Centrum Medyczne Pratia Katowice
Katowice
Centrum Medyczne Plejady
Krakow
Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie
Krakow
Specjalistyczny Gabinet Dermatologiczno-Kosmetyczny
Krakow
Oddział Kardiologiczny, WSS im. W. Biegańskiego w Łodzi
Lodz
Polimedica
Lodz
Pratia S,A
Warsaw
Reumatika- Centrum Reumatologii
Warsaw
Romania6 sites
Clinica Medicală Data Plus SRL
Bucharest, Sector 1
Institutul Clinic Fundeni
Bucharest, Sector 2
S.C. Centrul Medical Sana S.R.L.
Bucharest
S.C. Cardiomed S.R.L.
Craiova
Cabinet Medical Medicina Interna
Timișoara
Institutul de Boli Cardiovasculare Clinica de Cardiologie si Recuperare Cardiovasculara
Timișoara
Italy4 sites
Presidio Ospedaliero San Filippo e Nicola Università degli Studi dell'Aquila U.O.C Geriatria e Lungodegenza Geriatrica
Avezzano, L'Aquila, 67051
Azienda Ospedaliero-Universitaria Policlinico Sant'Orsola-Malpighi
Bologna, 40138
Ospedale Policlinico SS. Annunziata Università degli Studi "G. d'Annunzio". Dipartimento di Medicina e Scienze dell'Invecchiamento.
Chieti, 66100
Ospedale San Salvatore U.O.C. Medicina Interna e Nefrologia Dipartimento MeSVA Università degli Studi dell'Aquila
Coppito, L'Aquila, 67100
Serbia4 sites
Institut za kardiovaskularne bolesti Dedinje
Belgrade
Institut za reumatologiju
Belgrade
Kliničko-bolnički centar "Bežanijska kosa" Klinika za imunologiju i alergologiju
Belgrade
Vojnomedicinska akademija Klinika za reumatologiju
Belgrade
Germany1 site
Medizinische Klinik und Poliklinik III/Rheumatologie Universitätsklinikum "Carl Gustav Carus" Der Technischen Universität
Dresden, 01307
About this study
Official 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
There is a mounting and clear association between hyperuricaemia, gout and the presence of traditional cardiovascular (CV) risk factors and CV event-equivalent conditions such as chronic kidney disease, metabolic syndrome, and diabetes. Gout is associated with increased risk of CV events such as myocardial infarction and CV death. Furthermore hyperuricaemia is clearly associated with an increased arterial stiffness, a marker of pre-clinical atherosclerosis. Carotid-femoral pulse wave velocity (PWV) is the "gold standard" measurement of arterial stiffness and it is considered, in this trial, as a valid surrogate endpoint with clearly established relevance to predict cardiovascular disease (CVD) clinical outcome In this randomised trial conducted on adult subjects with a history of gout, we use surrogate endpoints to investigate the efficacy of febuxostat compared with allopurinol to predict (CVD) clinical outcome.
Eligible subjects were randomised in a 1:1 ratio to the following treatment groups:
Read more
- Test product: febuxostat 80 mg or 120 mg once daily (120 mg daily, if serum urate was >6 mg/dL after 2 weeks of treatment at 80 mg daily).
- Active comparator: allopurinol 100 mg once daily (up to a maximum dose of 600 mg daily escalated in 100 mg increments every 2 weeks, if serum urate acid (sUA) was >6 mg/dL after 2 weeks of treatment at the previous dose).
The study duration was 39 weeks, which included the:
- Run-in/screening period: 1 week (extendable up to a maximum of 30 days according to variability of sUA levels);
- Treatment period: 36 weeks;
- Safety follow-up period: 2 weeks.
Read the detailed description
The study physician, responsible for randomization and drug supply handling, is unblinded to study medications and therefore will not be involved in the main efficacy evaluations of each patient randomized in the study.
Conversely, the study physician/s responsible for the main efficacy evaluation (Pulse Wave Velocity) will be blind to study treatments.
Key efficacy variables will be performed by an independent centralized laboratory.
Trial was conducted in a detailed and orderly manner in accordance with established research principles, International Conference on Harmonization (ICH), Good Clinical Practice (GCP) Guidelines and with Clinical Research Organization (CRO) Standard Operating Procedures (SOPs). As part of a concerted effort to fulfill these obligations, the authorised CRO study monitor visited investigative sites prior to and during the trial in addition to maintaining telephone and written communication. Data from each subject were reviewed and source verified as the study progressed.
In accordance with audit plans, this trial may have been selected for audits. The investigators committed to permit independent audits by auditors assigned by the Sponsor at a reasonable notice. Audits included, but were not limited to, drug supply, presence of required documents, the informed consent process, protection of rights and well-being of subjects and verification of Electronic case report form (eCRF) entries against source documents.
Regulatory authorities worldwide had the right to inspect the investigative sites during or after the trial. In such cases, the investigators were required to contact the Sponsor immediately and to fully cooperate with the inspectors.
Copies of written correspondence between the investigators, CRO, Sponsor, Competent Authorities, Institutional Review Board (IRB) and Independent Ethic Committee (IEC) are on file with the Sponsor and investigators.
Adverse events were according to the Medical Dictionary for Regulatory Activities (MedDRA, version 18.0) thesaurus.
Statistical analysis were conducted according the Statistical Analysis Plan (SAP) describing the analytical principles and statistical techniques employed in order to address the objectives specified in the Protocol.
A Data Management Plan was present for missing data, to address situations where variables are reported as missing, unavailable, non-reported, uninterpretable, or considered missing because of data inconsistency or out-of-range results.
- Conditions
- Gout
- Being tested
- Febuxostat 80/120mg/day, Allopurinol 100 up to 600mg/day, Colchicine, Naproxen, Omeprazole
- Keywords
- Biological Markers, Cardiovascular disease, Humans, Pulse Wave Velocity, Cardiovascular risk factors, Allopurinol, Pulse Wave Analysis, Thiazoles, Inflammation, Uric acid, Febuxostat, Oxidative stress, Tumor Necrosis Factor, Arthritis, Hyperuricemia
- Medical subject headings
- Gout, Cardiovascular Diseases, Inflammation, Arthritis, Hyperuricemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Febuxostat 80/120mg/dayDrug
Also called Adenuric
Starting dose and dose regimen of Febuxostat : the initial daily dose is 80 mg. In case the patient has the serum urate concentration > 6 mg/dl after 2 weeks of treatment the dose will be escalated to 120 mg and if tolerated will be maintained for the duration of the study.
Allopurinol 100 up to 600mg/dayDrug
Also called Allopurinol
Starting dose and dose regimen of allopurinol : the initial daily allopurinol dose is 100 mg, to be increased by 100 mg every 2 weeks in patients with serum urate concentration >6 mg/dl. The maximum daily dose of allopurinol achievable in the study will depend on kidney function and tolerability, but will not exceed 600 mg.
ColchicineDrug
Colchicine 0.5 mg tablets.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD
NaproxenDrug
Also called Synflex
Naproxen sodium 550 mg film coated tablets. In case of colchicine intolerance patients will be treated for at least 6 months with Naproxen 550 mg BID and Omeprazole (20-40 mg once daily), if indicated to be used.
OmeprazoleDrug
Also called Omeprazen
Omeprazole 20 mg capsules, co-administered to patients for gastric protection.
| Study group | Role | What they receive |
|---|---|---|
| Febuxostat 80/120 mg/day | Experimental | Febuxostat 80/120 mg film coated tablets.The initial daily dose is 80 mg given orally. In case a patient has serum urate level 6 mg/dl after 2 weeks of treatment the dose will be escalated to 120 mg and if tolerated will be maintained during the study treatment period.
To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg quaque die (QD ) or in case of colchicine intolerance, Naproxen 550 mg bis in die (BID) with Omeprazole (20-40 mg once daily), if indicated to be used. Receives: Drug: Febuxostat 80/120mg/day; Drug: Colchicine; Drug: Naproxen; Drug: Omeprazole |
| Allopurinol 100 up to 600 mg/day | Active comparator | Allopurinol 100/300 mg tablets.The initial daily allopurinol dose is 100 mg given orally, to be escalated of 100 mg every 2 weeks in patients with serum urate concentration >6 mg/dl.
The maximum dose of allopurinol achievable in the study will depend on kidney function and tolerability, but will not exceed 600 mg daily.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD or in case of colchicine intolerance, Naproxen 550 mg BID with Omeprazole (20-40 mg once daily), if indicated to be used. Receives: Drug: Allopurinol 100 up to 600mg/day; Drug: Colchicine; Drug: Naproxen; Drug: Omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulse Wave Velocity
Comparison of the effects of Febuxostat and Allopurinol on Pulse Wave Velocity (PWV) after 36 weeks of treatment.
Measured: 36 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study start17 Aug 2015
- Primary completion10 May 2017
- Study completion10 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GoutStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini International Operations Luxembourg SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Claudio Borghi, Prof, Study director, Policlinico S.Orsola - Malpighi Medicina Interna Borghi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02500641
- Sponsor's protocol ID
- MEIN/14/FEB-PWV/001
- Other IDs
- 2014-005567-33, 2014
- Acronym
- FORWARD
- Status last verified
- Mar 2019
- First submitted
- 7 Jul 2015
- Last updated
- 21 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02500641
- Acronym / sponsor ID
- FORWARD / MEIN/14/FEB-PWV/001
- Conditions
- Gout
- Keywords
- Biological Markers, Cardiovascular disease, Humans, Pulse Wave Velocity, Cardiovascular risk factors, Allopurinol, Pulse Wave Analysis, Thiazoles
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Menarini International Operations Luxembourg SAIndustry (pharma, biotech, devices)
- Study start
- 17 Aug 2015 (actual)
- Primary completion
- 10 May 2017 (actual)
- Study completion
- 10 May 2017 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Posted 21 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is a mounting and clear association between hyperuricaemia, gout and the presence of traditional cardiovascular (CV) risk factors and CV event-equivalent conditions such as chronic kidney disease, metabolic syndrome, and diabetes. Gout is associated with increased risk of CV events such as myocardial infarction and CV death. Furthermore hyperuricaemia is clearly associated with an increased arterial stiffness, a marker of pre-clinical atherosclerosis. Carotid-femoral pulse wave velocity (PWV) is the "gold standard" measurement of arterial stiffness and it is considered, in this trial, as a valid surrogate endpoint with clearly established relevance to predict cardiovascular disease (CVD) clinical outcome In this randomised trial conducted on adult subjects with a history of gout, we use surrogate endpoints to investigate the efficacy of febuxostat compared with allopurinol to predict (CVD) clinical outcome.
Eligible subjects were randomised in a 1:1 ratio to the following treatment groups:
- Test product: febuxostat 80 mg or 120 mg once daily (120 mg daily, if serum urate was >6 mg/dL after 2 weeks of treatment at 80 mg daily).
- Active comparator: allopurinol 100 mg once daily (up to a maximum dose of 600 mg daily escalated in 100 mg increments every 2 weeks, if serum urate acid (sUA) was >6 mg/dL after 2 weeks of treatment at the previous dose).
The study duration was 39 weeks, which included the:
- Run-in/screening period: 1 week (extendable up to a maximum of 30 days according to variability of sUA levels);
- Treatment period: 36 weeks;
- Safety follow-up period: 2 weeks.
Detailed description
The study physician, responsible for randomization and drug supply handling, is unblinded to study medications and therefore will not be involved in the main efficacy evaluations of each patient randomized in the study.
Conversely, the study physician/s responsible for the main efficacy evaluation (Pulse Wave Velocity) will be blind to study treatments.
Key efficacy variables will be performed by an independent centralized laboratory.
Trial was conducted in a detailed and orderly manner in accordance with established research principles, International Conference on Harmonization (ICH), Good Clinical Practice (GCP) Guidelines and with Clinical Research Organization (CRO) Standard Operating Procedures (SOPs). As part of a concerted effort to fulfill these obligations, the authorised CRO study monitor visited investigative sites prior to and during the trial in addition to maintaining telephone and written communication. Data from each subject were reviewed and source verified as the study progressed.
In accordance with audit plans, this trial may have been selected for audits. The investigators committed to permit independent audits by auditors assigned by the Sponsor at a reasonable notice. Audits included, but were not limited to, drug supply, presence of required documents, the informed consent process, protection of rights and well-being of subjects and verification of Electronic case report form (eCRF) entries against source documents.
Regulatory authorities worldwide had the right to inspect the investigative sites during or after the trial. In such cases, the investigators were required to contact the Sponsor immediately and to fully cooperate with the inspectors.
Copies of written correspondence between the investigators, CRO, Sponsor, Competent Authorities, Institutional Review Board (IRB) and Independent Ethic Committee (IEC) are on file with the Sponsor and investigators.
Adverse events were according to the Medical Dictionary for Regulatory Activities (MedDRA, version 18.0) thesaurus.
Statistical analysis were conducted according the Statistical Analysis Plan (SAP) describing the analytical principles and statistical techniques employed in order to address the objectives specified in the Protocol.
A Data Management Plan was present for missing data, to address situations where variables are reported as missing, unavailable, non-reported, uninterpretable, or considered missing because of data inconsistency or out-of-range results.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Febuxostat 80/120 mg/day | Experimental | Drug: Febuxostat 80/120mg/day, Drug: Colchicine, Drug: Naproxen, Drug: OmeprazoleFebuxostat 80/120 mg film coated tablets.The initial daily dose is 80 mg given orally. In case a patient has serum urate level 6 mg/dl after 2 weeks of treatment the dose will be escalated to 120 mg and if tolerated will be maintained during the study treatment period. To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg quaque die (QD ) or in case of colchicine intolerance, Naproxen 550 mg bis in die (BID) with Omeprazole (20-40 mg once daily), if indicated to be used. |
| Allopurinol 100 up to 600 mg/day | Active comparator | Drug: Allopurinol 100 up to 600mg/day, Drug: Colchicine, Drug: Naproxen, Drug: OmeprazoleAllopurinol 100/300 mg tablets.The initial daily allopurinol dose is 100 mg given orally, to be escalated of 100 mg every 2 weeks in patients with serum urate concentration >6 mg/dl. The maximum dose of allopurinol achievable in the study will depend on kidney function and tolerability, but will not exceed 600 mg daily.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD or in case of colchicine intolerance, Naproxen 550 mg BID with Omeprazole (20-40 mg once daily), if indicated to be used. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female patients 18 years and older;
- History of gout, flare free in the 4 weeks prior to study entry
- 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%.
Key exclusion criteria (31 listed)
- Severe chronic renal failure (creatinine clearance < 30 ml/min)
- Hepatic failure
- Active liver disease or hepatic dysfunction, defined as both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 times the upper limit of normal.
- Diabetes mellitus type1
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Febuxostat 80/120mg/dayAlso: AdenuricStarting dose and dose regimen of Febuxostat : the initial daily dose is 80 mg. In case the patient has the serum urate concentration > 6 mg/dl after 2 weeks of treatment the dose will be escalated to 120 mg and if tolerated will be maintained for the duration of the study. | Drug | Febuxostat 80/120 mg/day |
| Allopurinol 100 up to 600mg/dayAlso: AllopurinolStarting dose and dose regimen of allopurinol : the initial daily allopurinol dose is 100 mg, to be increased by 100 mg every 2 weeks in patients with serum urate concentration >6 mg/dl. The maximum daily dose of allopurinol achievable in the study will depend on kidney function and tolerability, but will not exceed 600 mg. | Drug | Allopurinol 100 up to 600 mg/day |
| ColchicineColchicine 0.5 mg tablets.To prevent flares in the initial stages of treatment, patients will be treated for at least 6 months with colchicine 0.5 - 1 mg QD | Drug | Allopurinol 100 up to 600 mg/day, Febuxostat 80/120 mg/day |
| NaproxenAlso: SynflexNaproxen sodium 550 mg film coated tablets. In case of colchicine intolerance patients will be treated for at least 6 months with Naproxen 550 mg BID and Omeprazole (20-40 mg once daily), if indicated to be used. | Drug | Allopurinol 100 up to 600 mg/day, Febuxostat 80/120 mg/day |
| OmeprazoleAlso: OmeprazenOmeprazole 20 mg capsules, co-administered to patients for gastric protection. | Drug | Allopurinol 100 up to 600 mg/day, Febuxostat 80/120 mg/day |
Primary outcome
Pulse Wave Velocity
Time frame: 36 weeks of treatment
Comparison of the effects of Febuxostat and Allopurinol on Pulse Wave Velocity (PWV) after 36 weeks of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudio Borghi, Prof study director
Policlinico S.Orsola - Malpighi Medicina Interna Borghi
26 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Febuxostat 80/120mg/day, Allopurinol 100 up to 600mg/day and Colchicine in people with Gout, run by Menarini International Operations Luxembourg SA at 26 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Poland, Romania, Italy, Serbia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulse Wave Velocity (time frame: 36 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2019.