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You searched for 'ischemia'. Your search returned 6 results.

Multi-centre randomised controlled trial of clinical and cost-effectiveness of drug coated balloons, drug eluting stents and plain balloon angioplasty with bail-out bare metal stent revascularisation strategies for severe limb ischaemia due to atherosclerotic femoro-popliteal, with or without infra-popliteal involvement, peripheral arterial disease

Summary:
One in every 1000-2000 people in the UK will be diagnosed with advanced cases of Severe Limb Ischemia (SLI) yearly. As a result of a combination of smoking, diabetes mellitus, high blood pressure, high cholesterol levels, kidney failure and the ageing process, some people develop atherosclerosis (aka ‘hardening’ of the arteries) in their legs. In SLI even minor injuries to the foot can fail to heal, resulting in the development of ulceration, even gangrene.
Unless the blood supply to the leg and foot is improved, many people affected by SLI will lose their limb and/or die within 12 months. As well as causing great suffering, SLI places a large economic burden upon health (NHS) and social care services.
Most SLI patients with disease in the femoro-popliteal arteries are treated by endovascular means, which involves opening up the diseased arteries with balloons and sometimes the use of metal tubes called stents. In recent years, a number of “advanced” endovascular technologies – drug eluting stent (DES) and drug coated balloons (DCB) – have become available but the evidence base for using these new technologies is weak and they are much more expensive than the traditional methods.

The purpose of BASIL-3 is to determine which treatment is best at preventing amputation and death, getting the ulcers and gangrene to heal, and relieving pain in people with SLI. The costs of the 3 revascularisation strategies will be studied to see which offers the best value for money for the NHS.

Inclusion criteria:
In order to be considered for randomisation in BASIL-3, patients must:
•Have severe limb ischaemia due to femoro-popliteal, with or without infra-popliteal, peripheral artery disease
•Be judged by the responsible clinicians (consultant vascular surgeon, interventional radiologist, diabetologist) working as part of a multidisciplinary team to require early endovascular femoro-popliteal, with or without infrapopliteal revascularisation in addition to best medical treatment, foot and wound care
•Have adequate ‘inflow’ to support all possible trial revascularisation strategies
•Be judged suitable for all possible trial revascularisation strategies following diagnostic imaging and a formal
(documented) discussion by a multi-disciplinary team meeting.

Exclusion criteria:
Patient will be excluded from BASIL-3 if they
•Have an anticipated life expectancy Principal Investigator for this trial: Dr Said Habib

Research Ethics Committee Reference: 15/NS/0070

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

TAMARIN – Effects of TAMoxifen on the Mutant Allele Burden and Disease Course in Patients with MyeloprolifeRatIve Neoplasms

Summary:
Myeloproliferative neoplasms (MPNs) are blood cancers which affect the normal production of blood cells from the bone marrow. They are caused by changes (mutations) in blood stem cells, frequently in the genes that produce proteins called JAK2, CALR or MPL. MPNs have a risk of developing to an acute leukaemia (a more advanced stage of disease) and currently has no effective cure, apart from bone marrow transplantation which is not possible for many patients.
Recent work in mouse studies has suggested that tamoxifen, a drug widely used to treatment breast cancer, may reduce the number of mutated cells by mimicking oestrogen (a female sex hormone) which has a role in the survival and production of new stem cells that give rise to blood cancers. In these studies, tamoxifen prevented the excessive production of blood cells by restoring normal levels of cell death in the mutated cells.
This is a single arm, multicentre phase II trial designed to assess if adding tamoxifen to patients receiving therapy for their MPN reduces the number of mutated cells found in the blood by ≥ 50% after 24 weeks of treatment compared to the start of the study. Collection of blood and bone marrow samples will also allow laboratory researchers to study the biological effects of tamoxifen and how this correlates with the patient’s disease and response to therapy.
Patients will receive treatment with 20mg once daily (oral tablet) of tamoxifen with their normal therapy for their MPN. 42 patients will be recruited from 13-15 UK centres over 12 months.

Inclusion criteria:
• Age ≥ 60 years (men aged between 50-59 may also be considered following discussion with the Chief Investigator)
• Women must be post-menopausal (defined as amenorrhoeic for at least 12 consecutive months following cessation of all exogenous hormonal treatments)
• Confirmed diagnosis of JAK2-V617F or CALR positive Essential Thrombocythaemia (ET), Polycythaemia Vera (PV) or Myelofibrosis (MF) (primary or secondary) for ≥ 6 months
• JAK2-V617F or CALR mutant allele burden ≥ 20% in peripheral blood granulocyte DNA at study entry (assessed via central review)
• WHO performance status 0-2
• For patients with PV or ET, maintenance of at least a partial haematological response according to 2009 ELN criteria must have been achieved for the previous 6 months (prior to registration), without introduction of any new therapeutic agents for their MPN
• For patients with MF, there must not have been any evidence of disease progression* for the previous 6 months (prior to registration) and no new therapeutic agents for their MPN introduced during this period.
• Patients receiving cytoreductive therapy for their MPN (not solely aspirin or venesection)
• Adequate hepatic function, defined as:
o bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with elevated bilirubin due to Gilbert’s syndrome are eligible)
o AST/ALT/ALP ≤ 2.5 x ULN
• Adequate renal function (creatinine clearance >30 mL/min)
• Male patients must agree to use effective contraception during participation in the trial and for 2 months after the last dose of trial treatment
• Patient must be able to give written informed consent
*Defined by IWG-MRT ELN criteria (Appendix 6). Please note no baseline bone marrow is required to confirm absence of “Leukemic transformation confirmed by a bone marrow blast count of ≥20%”.

Exclusion criteria:
• Leukaemic transformation (>20% blasts in blood, marrow or extramedullary site).
• Accelerated phase of disease as indicated by >5% blasts in the peripheral blood
• Treatment of ET, PV or MF with Interferon alpha or JAK inhibitors, such as ruxolitinib, or other investigational agents for their MPN within 6 months prior to trial entry
• Any of the following previous thrombotic events at any time:
o Portal or other splanchnic venous thrombosis
o Vascular access complication
o Ischemia cerebrovascular
o Stroke
o Transient Ischaemic attack
o Superficial thrombophlebitis
o Venous Thromboembolic events including pulmonary embolism (PE) and deep vein thrombosis (DVT)
o Peripheral vascular ischemia
o Visceral arterial ischemia
o Acute coronary syndrome
o Myocardial infarction
• Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
• Previous endometrial cancer, hyperplasia or polyps
• Prior treatment with hematopoietic stem cell transplantation
• Patients who do not carry any mutations in JAK2V617F or CALR or allele burden grade 1
• Any serious underlying medical condition (at the judgment of the Investigator), which could impair the ability of the patient to participate in the trial (e.g. liver disease, active autoimmune disease, uncontrolled diabetes, uncontrolled infection (HIV, Hepatitis B and C), known genetic defect (apart from MPN) relating to venous thromboembolic events, or psychiatric disorder precluding understanding of trial information)
• Known hypersensitivity to tamoxifen or hypersensitivity to any other component of tamoxifen
• Concomitant drugs contraindicated for use with the trial drug according to the Summary of Product Characteristics
• Known planned scheduled elective surgery during study with the exception of dental and low risk eye surgery (e.g. cataracts)

Principal Investigator for this trial: Professor Nigel Russell

Research Ethics Committee Reference: 16/EM/0181

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects with Nonalcoholic Steatohepatitis

Summary:
This study will evaluate the Safety and Efficacy of Obeticholic Acid (OCA) in Subjects with Nonalcoholic Steatohepatitis (NASH).
NASH is a serious, chronic liver disease with a large unmet medical need and no approved treatments. The incidence of NASH is increasing and NASH is likely to be the leading cause of liver transplant by 2020.
In view of the serious nature of the disease, the increasing number of patients, the complications that arise from the disease,and the unmet medical need, approved therapy for NASH is needed.
The Sponsor of this study, Intercept Pharmaceuticals, Inc., wants to study the investigational drug OCA and its effect on NASH.
OCA, is a modified (manmade) version of a compound made in the liver called a bile acid. Bile acids are used by the body to help with digestion and have additional effects on liver function. This study will look at the effect of OCA onimprovements in the condition of liver tissue for patients with NASH, all-cause mortality, and liver-related clinical outcomes.
Up to 300 medical centers in Latin America, North America, Asia Pacific Region and Europe are expected to participate in this study.
Subjects will be screened for a period of up to 12 weeks before entering the study. Approximately 2065 subjects
(globally) with NASH will be randomized to receive OCA 10 mg, OCA 25 mg, or matching placebo in a 1:1:1 ratio for the duration of the study, in conjunction with local standard of care.
Once participation in the study is confirmed, patients will attend the clinic 8 times for the first 18 months they are in the study and then 2 times per year (every 6 months) for each additional year they are in the study.
The expected duration of this study is approx. 6 years.
Intercept Pharmaceuticals, Inc., a drug company, is funding the study.

Inclusion criteria:
1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by presence of all 3 key histological features of NASH with a score of at least 1 for each and a combined score of 4 or greater out of a possible 8 points according to NASH CRN criteria.
2. Histologic evidence of fibrosis stage 2 (perisinusoidal and portal/periportal) or stage 3 (bridging fibrosis) as defined by the NASH CRN scoring of fibrosis, or Histologic evidence of fibrosis stage 1a or stage 1b (mild or moderate, zone 3 perisinusoidal) as defined by the NASH CRN scoring of fibrosis if accompanied by ≥1 of the following risk factors:
– Obesity (body mass index ≥30 kg/m2)
– Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria(hemoglobin A1c [HbA1c]
≥6.5%, fasting plasma glucose ≥126 mg/dL, 2-hour
plasma glucose ≥200 mg/dL during oral glucose tolerance test, or random plasma glucose ≥200 mg/dL)
– Alanine aminotransferase >1.5 x upper limit of normal (ULN).
3. Is either not taking or is on stable doses of :
– − TZDs or vitamin E for 6 months before Day 1
– Therapies for diabetes (excluding TZDs) and weight loss for 90 days before Day 1
– Allowed concomitant medications and supplements for 30 days before Day 1.
4. Stable body weight (ie, not varying by >10% for at least 3 months) before Day 1.
5. Age ≥18 years.
6. Female subjects of childbearing potential must use ≥1 effective method of contraception during the study and until 30 days following the last dose of investigational product. Effective methods of contraception are considered to be those listed below
– Double barrier method, ie, condom (male or female) or diaphragm with spermicide
– Intrauterine device
– Vasectomy (partner)
– Hormonal (eg, contraceptive pill, patch, intramuscular implant or injection)
– Abstinence (defined as refraining from heterosexual intercourse)
7. Must provide written informed consent and agree to comply with the study protocol.

Exclusion criteria:
1. Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year before Screening (significant alcohol consumption is defined as more than 2 units/day for females and more than 4 units/day for males, on average).
2. Prior or planned (during the study period) bariatric surgery (eg, gastric bands, gastroplasty, roux-en-Y
gastric bypass) or ileal resection.
3. HbA1c ≥9.0% within 60 days before Day 1.
4. Evidence of other forms of chronic liver disease including:
– Positive test result at Screening for hepatitis B surface antigen or hepatitis C antibody (and positive HCV ribonucleic acid [RNA])
– Primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndrome
– Alcoholic liver disease
– Wilson’s disease, hemochromatosis, or iron overload
– Alpha-1-antitrypsin (A1AT) deficiency as defined by diagnostic features in liver histology (confirmed by A1AT level below the lower limit of normal or exclusion at the Investigator’s discretion)
– Prior known drug-induced liver injury within 5 years before Day 1
– Known or suspected HCC
– History of liver transplant, current placement on a liver transplant list, or current MELD score >12
5. Histological presence of cirrhosis.
6. Total bilirubin >1.5 mg/dL at Screening (subjects with Gilbert’s syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated bilirubin is 10× ULN, international normalized ratio (INR) >1.3, or serum creatinine ≥1.5 mg/dL at Screening.
8. Creatine phosphokinase >5 x ULN at Screening.
9. Platelet count Principal Investigator for this trial: Professor Guruprasad P Aithal

Research Ethics Committee Reference: 15/YH/0478

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects with Nonalcoholic Steatohepatitis

Summary:
This study will evaluate the Safety and Efficacy of Obeticholic Acid (OCA) in Subjects with Nonalcoholic Steatohepatitis (NASH).
NASH is a serious, chronic liver disease with a large unmet medical need and no approved treatments. The incidence of NASH is increasing and NASH is likely to be the leading cause of liver transplant by 2020.
In view of the serious nature of the disease, the increasing number of patients, the complications that arise from the disease,and the unmet medical need, approved therapy for NASH is needed.
The Sponsor of this study, Intercept Pharmaceuticals, Inc., wants to study the investigational drug OCA and its effect on NASH.
OCA, is a modified (manmade) version of a compound made in the liver called a bile acid. Bile acids are used by the body to help with digestion and have additional effects on liver function. This study will look at the effect of OCA onimprovements in the condition of liver tissue for patients with NASH, all-cause mortality, and liver-related clinical outcomes.
Up to 300 medical centers in Latin America, North America, Asia Pacific Region and Europe are expected to participate in this study.
Subjects will be screened for a period of up to 12 weeks before entering the study. Approximately 2065 subjects
(globally) with NASH will be randomized to receive OCA 10 mg, OCA 25 mg, or matching placebo in a 1:1:1 ratio for the duration of the study, in conjunction with local standard of care.
Once participation in the study is confirmed, patients will attend the clinic 8 times for the first 18 months they are in the study and then 2 times per year (every 6 months) for each additional year they are in the study.
The expected duration of this study is approx. 6 years.
Intercept Pharmaceuticals, Inc., a drug company, is funding the study.

Inclusion criteria:
1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by presence of all 3 key histological features of NASH with a score of at least 1 for each and a combined score of 4 or greater out of a possible 8 points according to NASH CRN criteria.
2. Histologic evidence of fibrosis stage 2 (perisinusoidal and portal/periportal) or stage 3 (bridging fibrosis) as defined by the NASH CRN scoring of fibrosis, or Histologic evidence of fibrosis stage 1a or stage 1b (mild or moderate, zone 3 perisinusoidal) as defined by the NASH CRN scoring of fibrosis if accompanied by ≥1 of the following risk factors:
– Obesity (body mass index ≥30 kg/m2)
– Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria(hemoglobin A1c [HbA1c]
≥6.5%, fasting plasma glucose ≥126 mg/dL, 2-hour
plasma glucose ≥200 mg/dL during oral glucose tolerance test, or random plasma glucose ≥200 mg/dL)
– Alanine aminotransferase >1.5 x upper limit of normal (ULN).
3. Is either not taking or is on stable doses of :
– − TZDs or vitamin E for 6 months before Day 1
– Therapies for diabetes (excluding TZDs) and weight loss for 90 days before Day 1
– Allowed concomitant medications and supplements for 30 days before Day 1.
4. Stable body weight (ie, not varying by >10% for at least 3 months) before Day 1.
5. Age ≥18 years.
6. Female subjects of childbearing potential must use ≥1 effective method of contraception during the study and until 30 days following the last dose of investigational product. Effective methods of contraception are considered to be those listed below
– Double barrier method, ie, condom (male or female) or diaphragm with spermicide
– Intrauterine device
– Vasectomy (partner)
– Hormonal (eg, contraceptive pill, patch, intramuscular implant or injection)
– Abstinence (defined as refraining from heterosexual intercourse)
7. Must provide written informed consent and agree to comply with the study protocol.

Exclusion criteria:
1. Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year before Screening (significant alcohol consumption is defined as more than 2 units/day for females and more than 4 units/day for males, on average).
2. Prior or planned (during the study period) bariatric surgery (eg, gastric bands, gastroplasty, roux-en-Y
gastric bypass) or ileal resection.
3. HbA1c ≥9.0% within 60 days before Day 1.
4. Evidence of other forms of chronic liver disease including:
– Positive test result at Screening for hepatitis B surface antigen or hepatitis C antibody (and positive HCV ribonucleic acid [RNA])
– Primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndrome
– Alcoholic liver disease
– Wilson’s disease, hemochromatosis, or iron overload
– Alpha-1-antitrypsin (A1AT) deficiency as defined by diagnostic features in liver histology (confirmed by A1AT level below the lower limit of normal or exclusion at the Investigator’s discretion)
– Prior known drug-induced liver injury within 5 years before Day 1
– Known or suspected HCC
– History of liver transplant, current placement on a liver transplant list, or current MELD score >12
5. Histological presence of cirrhosis.
6. Total bilirubin >1.5 mg/dL at Screening (subjects with Gilbert’s syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated bilirubin is 10× ULN, international normalized ratio (INR) >1.3, or serum creatinine ≥1.5 mg/dL at Screening.
8. Creatine phosphokinase >5 x ULN at Screening.
9. Platelet count Principal Investigator for this trial: Professor Guruprasad P Aithal

Research Ethics Committee Reference: 15/YH/0478

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

International Study of Comparative Health Effectiveness with Medical invasive Approaches

Summary:
Coronary artery disease remains the leading global cause of death and disability. However there is still no conclusive
evidence to indicate an optimal strategy for early management of patients with stable coronary artery disease to reduce
long term clinical outcomes.
ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) is an
international, randomised controlled trial comparing the effectiveness of two initial management strategies for patients
diagnosed with stable ischemic heart disease. Management is either early invasive (cardiac catheterization followed
by optimal revascularisation of narrowing of coronary arteries, plus optimal medical therapy), or conservative (optimal
medical therapy and only cardiac catheterization performed if there is a decline in their clinical symptoms). Prior to
enrolment, patients must display evidence (via imaging tests) of moderate to severe impairment of blood supply to
their heart muscle. All patients enrolled will undergo coronary CT angiography unless they have a renal contra
indication.
Enrolment is expected to be over a 4 year period with a minimum 1.5 year follow up period. Patients randomised to
the invasive group will undergo optimal revascularisation (PCI or percutaneous coronary intervention = insertion of a
wire with a balloon into a coronary artery which is then inflated, or CABG (coronary artery bypass grafting = cardiac
surgery involving insertion of bypass grafts over diseased vessels which allows blood flow to cardiac muscle). The
choice of type of revascularisation will be made by the local interventional cardiologist, and cardiovascular surgeon
based on protocol recommendations. Patients who are randomised to optimal medical therapy and experience
deterioration in their condition are permitted to have invasive management which is the current recommendation for
patients experiencing an acute coronary syndrome (heart attack or unstable angina). The primary outcome measure
is a comparison of the composite endpoint of cardiovascular death or nonfatal heart attack between the two
strategies.

Inclusion criteria:
All patients 21 years who have stable ischemic heart disease and have ischemia eligibility as assessed by a core
laboratory: at least moderate ischemia on a stress test with nuclear myocardial perfusion imaging (10%
myocardium), echo wall motion (3/16 segments with stress-induced severe hypokinesis or akinesis), or cardiac
magnetic resonance perfusion (12% myocardium) or wall motion imaging (3/16 segments with stressinduced
severe hypokinesis or akinesis).
In addition, patients must be willing to comply with the protocol and provide informed consent.

Exclusion criteria:
· LVEF Principal Investigator for this trial: Dr Robert A Henderson

Research Ethics Committee Reference: 12/SS/0109

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

International Study of Comparative Health Effectiveness with Medical invasive Approaches

Summary:
Coronary artery disease remains the leading global cause of death and disability. However there is still no conclusive
evidence to indicate an optimal strategy for early management of patients with stable coronary artery disease to reduce
long term clinical outcomes.
ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) is an
international, randomised controlled trial comparing the effectiveness of two initial management strategies for patients
diagnosed with stable ischemic heart disease. Management is either early invasive (cardiac catheterization followed
by optimal revascularisation of narrowing of coronary arteries, plus optimal medical therapy), or conservative (optimal
medical therapy and only cardiac catheterization performed if there is a decline in their clinical symptoms). Prior to
enrolment, patients must display evidence (via imaging tests) of moderate to severe impairment of blood supply to
their heart muscle. All patients enrolled will undergo coronary CT angiography unless they have a renal contra
indication.
Enrolment is expected to be over a 4 year period with a minimum 1.5 year follow up period. Patients randomised to
the invasive group will undergo optimal revascularisation (PCI or percutaneous coronary intervention = insertion of a
wire with a balloon into a coronary artery which is then inflated, or CABG (coronary artery bypass grafting = cardiac
surgery involving insertion of bypass grafts over diseased vessels which allows blood flow to cardiac muscle). The
choice of type of revascularisation will be made by the local interventional cardiologist, and cardiovascular surgeon
based on protocol recommendations. Patients who are randomised to optimal medical therapy and experience
deterioration in their condition are permitted to have invasive management which is the current recommendation for
patients experiencing an acute coronary syndrome (heart attack or unstable angina). The primary outcome measure
is a comparison of the composite endpoint of cardiovascular death or nonfatal heart attack between the two
strategies.

Inclusion criteria:
All patients 21 years who have stable ischemic heart disease and have ischemia eligibility as assessed by a core
laboratory: at least moderate ischemia on a stress test with nuclear myocardial perfusion imaging (10%
myocardium), echo wall motion (3/16 segments with stress-induced severe hypokinesis or akinesis), or cardiac
magnetic resonance perfusion (12% myocardium) or wall motion imaging (3/16 segments with stressinduced
severe hypokinesis or akinesis).
In addition, patients must be willing to comply with the protocol and provide informed consent.

Exclusion criteria:
· LVEF Principal Investigator for this trial: Dr Robert A Henderson

Research Ethics Committee Reference: 12/SS/0109

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

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