Marfan SyndromePhase 3MaNeLoNCT00683124
Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
A Phase 3 study testing Losartan and nebivolol, Losartan and Nebivolol in people with Marfan Syndrome, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial summary
The major clinical problems in patients with Marfan Syndrome (MFS) are aortic root dilation (ARD), dissection and rupture. Although the available treatments (beta-blockers, BBs) improve the evolution of the disease, they do not protect MFS patients from progression of ARD and dissection. Read more about this study
- Who is it for?
- Ages 12 months to 55 years
- Conditions the study is for
- Marfan Syndrome
- What is being tested?
- Losartan and nebivolol, Losartan and Nebivolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 291 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2008to Jul 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 12 months to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of MFS: Ghent criteria and genetically proven defect of the FBN1 gene
- Age: 12 months to 55 years
- BSA-adjusted aortic z score = or >2 measured at the level of the sinuses of Valsalva at baseline according to Roman's method, or absolute aortic root diameter >38mm for females and >40 mm for males
Who cannot join
- Prior aortic surgery and/or dissection
- Aortic root diameter at the level of the sinuses of Valsalva 5 cm
- Planned aortic surgery within 6 months of enrollment for a rate of ARD progression>5 mm/year even in pts with ARD less than 5 cm
- Clinical or molecular diagnosis of non-MFS connective tissue diseases sharing some features with MFS (Shprintzen-Goldberg syndrome or Loeys-Dietz syndromes)
- Un-renounceable therapeutic (systemic hypertension, arrhythmia, ventricular dysfunction, valve regurgitation) use of drugs such as ACE inhibitors, BBs, or calcium-channel blockers
- Known side-effects while taking an ARB or a BB
Show all 13Show fewer
- Intolerance to ARB that resulted in termination of therapy
- Intolerance to BB that resulted in termination of therapy
- Renal dysfunction (creatinine level more than upper limit of age-related normal values)
- Diabetes mellitus
- Pregnancy or planned pregnancy within 48 months of enrollment
- Technical limitations for the imaging studies including poor acoustic windows with limits the accurate measurement of aortic root
- Asthma.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Foundation San Matteo Hospital
Pavia, 27100
Eloisa Arbustini, MD,FESC,FACC, +390382501206, e.arbustini@smatteo.pv.it
Fabiana I Gambarin, MD, +390382501206, f.gambarin@smatteo.pv.it
About this study
Official title: Effects of Losartan vs. Nebivolol vs. the Association of Both on the Progression of Aortic Root Dilation in Marfan Syndrome (MFS) With FBN1 Gene Mutations.
The major clinical problems in patients with Marfan Syndrome (MFS) are aortic root dilation (ARD), dissection and rupture. Although the available treatments (beta-blockers, BBs) improve the evolution of the disease, they do not protect MFS patients from progression of ARD and dissection. A key molecule that negatively influences cell growth, differentiation, survival and death in MFS is TGFb which is antagonised by existing drugs employed in the clinical practice, the Angiotensin II receptor blockers (ARB).
Read the detailed description
Marfan Syndrome is a rare disease (1:5000)(MIM#154700) caused by mutations of the Fibrillin 1 (FBN1) gene. The major clinical problem is aortic aneurysm with risk of dissection when root diameter is 5 cm.
The investigators designed a clinical trial in which a new generation Beta-Blocker Nebivolol with expected effects on shear stress, heart rate and potential anti-stiffness benefits is compared to Losartan, and Angiotensin receptor blocker anti TGF-beta effects, and to the association of both molecules in patients with Marfan Syndrome. Nebivolol is a patented drug that differs chemically, pharmacologically and therapeutically from all other BBs. Nebivolol shows the highest selectivity for ß1 receptors among the currently available BBs, influences the arterial stiffness through an agonistic effect on ß2-receptors and preserves the arterial compliance. We expect a significantly lower progression of the Aortic Root Dilation in the arm of Nebivolol plus Losartan vs. single drug (primary end-point).The investigators further expect: decrease of arterial stiffness higher in the arm treated with both drugs than in solely Nebivolol or Losartan; a decrease of serum levels of active TGFb in both Losartan arms, a drug \& age-dependant variation of the expression of the mutated FBN1 gene. As for other end-points, the potential results are the improvement of valve function, hard events \& delay of surgical timing for the aortic root. The enrolment period will last 12 months, while the overall follow-up period will be of 4 years. An interim analysis for the primary outcome is programmed at month 24.
- Conditions
- Marfan Syndrome
- Being tested
- Losartan and nebivolol, Losartan, Nebivolol
- Keywords
- Marfan Syndrome, Losartan, Nebivolol, Transforming Growth Factor Beta, Aortic Root Dilation
- Medical subject headings
- Marfan Syndrome, Camurati-Engelmann Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losartan and nebivololDrug
Nebivolol is administered orally as pills. It is given preferentially once a day in the morning or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations.
Losartan is administered orally as pills. It is given preferentially once a day or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations
LosartanDrug
Losartan is administered orally as pills. It is given preferentially once a day or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations
NebivololDrug
Nebivolol is administered orally as pills. It is given preferentially once a day in the morning or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | Losartan administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 100 mg/day for adults and 1,6 mg/kg/die for children minor than 16 years. Receives: Drug: Losartan |
| Nebivolol | Experimental | Nebivolol administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 10 mg/day for adults and 0,16 mg/kg/die for children minor than 16 years. Receives: Drug: Nebivolol |
| Losartan+Nebivolol | Experimental | Losartan administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 100 mg/day for adults and 1,6 mg/kg/die for children minor than 16 years.
Nebivolol administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 10 mg/day for adults and 0,16 mg/kg/die for children minor than 16 years. Receives: Drug: Losartan and nebivolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
BSA and age-adjusted aortic root diameter (sinuses of Valsalva)
Measured: every 12 months
Secondary outcomes (10)
The pharmacokinetics of the two drugs by age and dosages
Measured: every 12 months
Comparative evaluation of the serum levels of total and active TGFb
Measured: every 12 months
Quantitative assessment of the expression of the mutated gene (FBN1, both 5' and 3')
Measured: every 12 months
Pharmacogenetic bases of drug responsiveness (Losartan: CYP2C9 gene) (Nebivolol: CYP2D6 gene)
Measured: every 12 months
Aortic valve regurgitation severity
Measured: every 12 months
Left ventricular end-diastolic diameter
Measured: every 12 months
Left ventricular ejection fraction
Measured: every 12 months
Spirometric lung volumes and flows
Measured: every 12 months
QoL evaluation basing on SF-36 questionnaire
Measured: every 12 months
Arterial stiffness (carotids)
Measured: every 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2013 (estimated)
- Study completionJul 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Marfan SyndromeStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 291 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Menarini Group
- Investigators
- Eloisa Arbustini, MD,FESC,FACC, Principal investigator, IRCCS Foundation San Matteo Hospital, PaviaLuigi Tavazzi, MD,FESC,FACC, Study chair, IRCCS Foundation San Matteo Hospital, Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00683124
- Sponsor's protocol ID
- FARM7KP2PX
- Other IDs
- EudraCT 2008-001462-81
- Acronym
- MaNeLo
- Status last verified
- Jul 2011
- First submitted
- 21 May 2008
- Last updated
- 22 Jul 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int. 1997 May;51(5):1376-82. doi: 10.1038/ki.1997.188.
PubMed 9150447Hao J, Wang B, Jones SC, Jassal DS, Dixon IM. Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro. Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3020-30. doi: 10.1152/ajpheart.2000.279.6.H3020.
PubMed 11087260Border WA, Noble NA. Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension. 1998 Jan;31(1 Pt 2):181-8. doi: 10.1161/01.hyp.31.1.181.
PubMed 9453300Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, Roberts R, Marian AJ. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation. 2001 Feb 13;103(6):789-91. doi: 10.1161/01.cir.103.6.789.
PubMed 11171784Pauwels PJ, Gommeren W, Van Lommen G, Janssen PA, Leysen JE. The receptor binding profile of the new antihypertensive agent nebivolol and its stereoisomers compared with various beta-adrenergic blockers. Mol Pharmacol. 1988 Dec;34(6):843-51.
PubMed 2462161Ignarro LJ. Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third-generation beta-blocker. Blood Press Suppl. 2004 Oct;1:2-16.
PubMed 15587107McEniery CM, Schmitt M, Qasem A, Webb DJ, Avolio AP, Wilkinson IB, Cockcroft JR. Nebivolol increases arterial distensibility in vivo. Hypertension. 2004 Sep;44(3):305-10. doi: 10.1161/01.HYP.0000137983.45556.6e. Epub 2004 Jul 19.
PubMed 15262912Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
PubMed 1593914Van Bortel LM, Bulpitt CJ, Fici F. Quality of life and antihypertensive effect with nebivolol and losartan. Am J Hypertens. 2005 Aug;18(8):1060-6. doi: 10.1016/j.amjhyper.2005.03.733.
PubMed 16296572Mangrella M, Rossi F, Fici F, Rossi F. Pharmacology of nebivolol. Pharmacol Res. 1998 Dec;38(6):419-31. doi: 10.1006/phrs.1998.0387.
PubMed 9990650Roman MJ, Devereux RB, Kramer-Fox R, O'Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol. 1989 Sep 1;64(8):507-12. doi: 10.1016/0002-9149(89)90430-x.
PubMed 2773795Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006 Apr 7;312(5770):117-21. doi: 10.1126/science.1124287.
PubMed 16601194Selamet Tierney ES, Feingold B, Printz BF, Park SC, Graham D, Kleinman CS, Mahnke CB, Timchak DM, Neches WH, Gersony WM. Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome. J Pediatr. 2007 Jan;150(1):77-82. doi: 10.1016/j.jpeds.2006.09.003.
PubMed 17188619Ahimastos AA, Aggarwal A, D'Orsa KM, Formosa MF, White AJ, Savarirayan R, Dart AM, Kingwell BA. Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial. JAMA. 2007 Oct 3;298(13):1539-47. doi: 10.1001/jama.298.13.1539.
PubMed 17911499Gambarin FI, Favalli V, Serio A, Regazzi M, Pasotti M, Klersy C, Dore R, Mannarino S, Vigano M, Odero A, Amato S, Tavazzi L, Arbustini E. Rationale and design of a trial evaluating the effects of losartan vs. nebivolol vs. the association of both on the progression of aortic root dilation in Marfan syndrome with FBN1 gene mutations. J Cardiovasc Med (Hagerstown). 2009 Apr;10(4):354-62. doi: 10.2459/JCM.0b013e3283232a45.
PubMed 19430350
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Losartan vs. Nebivolol vs. the Association of Both on the Progression of Aortic Root Dilation in Marfan Syndrome (MFS) With FBN1 Gene Mutations.
- ClinicalTrials.gov ID
- NCT00683124
- Acronym / sponsor ID
- MaNeLo / FARM7KP2PX
- Conditions
- Marfan Syndrome
- Keywords
- Marfan Syndrome, Losartan, Nebivolol, Transforming Growth Factor Beta, Aortic Root Dilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 291 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Menarini Group
- Study start
- Jul 2008
- Primary completion
- Jul 2013 (estimated)
- Study completion
- Jul 2013 (estimated)
- First posted
- 23 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The major clinical problems in patients with Marfan Syndrome (MFS) are aortic root dilation (ARD), dissection and rupture. Although the available treatments (beta-blockers, BBs) improve the evolution of the disease, they do not protect MFS patients from progression of ARD and dissection. A key molecule that negatively influences cell growth, differentiation, survival and death in MFS is TGFb which is antagonised by existing drugs employed in the clinical practice, the Angiotensin II receptor blockers (ARB).
Detailed description
Marfan Syndrome is a rare disease (1:5000)(MIM#154700) caused by mutations of the Fibrillin 1 (FBN1) gene. The major clinical problem is aortic aneurysm with risk of dissection when root diameter is 5 cm.
The investigators designed a clinical trial in which a new generation Beta-Blocker Nebivolol with expected effects on shear stress, heart rate and potential anti-stiffness benefits is compared to Losartan, and Angiotensin receptor blocker anti TGF-beta effects, and to the association of both molecules in patients with Marfan Syndrome. Nebivolol is a patented drug that differs chemically, pharmacologically and therapeutically from all other BBs. Nebivolol shows the highest selectivity for ß1 receptors among the currently available BBs, influences the arterial stiffness through an agonistic effect on ß2-receptors and preserves the arterial compliance. We expect a significantly lower progression of the Aortic Root Dilation in the arm of Nebivolol plus Losartan vs. single drug (primary end-point).The investigators further expect: decrease of arterial stiffness higher in the arm treated with both drugs than in solely Nebivolol or Losartan; a decrease of serum levels of active TGFb in both Losartan arms, a drug \& age-dependant variation of the expression of the mutated FBN1 gene. As for other end-points, the potential results are the improvement of valve function, hard events \& delay of surgical timing for the aortic root. The enrolment period will last 12 months, while the overall follow-up period will be of 4 years. An interim analysis for the primary outcome is programmed at month 24.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: LosartanLosartan administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 100 mg/day for adults and 1,6 mg/kg/die for children minor than 16 years. |
| Nebivolol | Experimental | Drug: NebivololNebivolol administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 10 mg/day for adults and 0,16 mg/kg/die for children minor than 16 years. |
| Losartan+Nebivolol | Experimental | Drug: Losartan and nebivololLosartan administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 100 mg/day for adults and 1,6 mg/kg/die for children minor than 16 years. Nebivolol administered as maximal tolerated dosage, not to exceed the maximal theorical dosage of 10 mg/day for adults and 0,16 mg/kg/die for children minor than 16 years. |
Who may qualify
- Ages
- 12 months to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Diagnosis of MFS: Ghent criteria and genetically proven defect of the FBN1 gene
- Age: 12 months to 55 years
- BSA-adjusted aortic z score = or >2 measured at the level of the sinuses of Valsalva at baseline according to Roman's method, or absolute aortic root diameter >38mm for females and >40 mm for males
Key exclusion criteria (13 listed)
- Prior aortic surgery and/or dissection
- Aortic root diameter at the level of the sinuses of Valsalva 5 cm
- Planned aortic surgery within 6 months of enrollment for a rate of ARD progression>5 mm/year even in pts with ARD less than 5 cm
- Clinical or molecular diagnosis of non-MFS connective tissue diseases sharing some features with MFS (Shprintzen-Goldberg syndrome or Loeys-Dietz syndromes)
- Un-renounceable therapeutic (systemic hypertension, arrhythmia, ventricular dysfunction, valve regurgitation) use of drugs such as ACE inhibitors, BBs, or calcium-channel blockers
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 |
|---|---|---|
| Losartan and nebivololNebivolol is administered orally as pills. It is given preferentially once a day in the morning or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations. Losartan is administered orally as pills. It is given preferentially once a day or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations | Drug | Losartan+Nebivolol |
| LosartanLosartan is administered orally as pills. It is given preferentially once a day or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations | Drug | Losartan |
| NebivololNebivolol is administered orally as pills. It is given preferentially once a day in the morning or, if not well tolerated because of hypotension, the total daily dosage is given in two administrations | Drug | Nebivolol |
Primary outcome
BSA and age-adjusted aortic root diameter (sinuses of Valsalva)
Time frame: every 12 months
10 secondary outcomes
The pharmacokinetics of the two drugs by age and dosages
Time frame: every 12 months
Comparative evaluation of the serum levels of total and active TGFb
Time frame: every 12 months
Quantitative assessment of the expression of the mutated gene (FBN1, both 5' and 3')
Time frame: every 12 months
Pharmacogenetic bases of drug responsiveness (Losartan: CYP2C9 gene) (Nebivolol: CYP2D6 gene)
Time frame: every 12 months
Aortic valve regurgitation severity
Time frame: every 12 months
Left ventricular end-diastolic diameter
Time frame: every 12 months
Left ventricular ejection fraction
Time frame: every 12 months
Spirometric lung volumes and flows
Time frame: every 12 months
QoL evaluation basing on SF-36 questionnaire
Time frame: every 12 months
Arterial stiffness (carotids)
Time frame: every 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2011.
- Background: PubMed 9150447Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int. 1997 May;51(5):1376-82. doi: 10.1038/ki.1997.188.
- Background: PubMed 11087260Hao J, Wang B, Jones SC, Jassal DS, Dixon IM. Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro. Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3020-30. doi: 10.1152/ajpheart.2000.279.6.H3020.
- Background: PubMed 9453300Border WA, Noble NA. Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension. 1998 Jan;31(1 Pt 2):181-8. doi: 10.1161/01.hyp.31.1.181.
- Background: PubMed 11171784Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, Roberts R, Marian AJ. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation. 2001 Feb 13;103(6):789-91. doi: 10.1161/01.cir.103.6.789.
- Background: PubMed 2462161Pauwels PJ, Gommeren W, Van Lommen G, Janssen PA, Leysen JE. The receptor binding profile of the new antihypertensive agent nebivolol and its stereoisomers compared with various beta-adrenergic blockers. Mol Pharmacol. 1988 Dec;34(6):843-51.
- Background: PubMed 15587107Ignarro LJ. Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third-generation beta-blocker. Blood Press Suppl. 2004 Oct;1:2-16.
- Background: PubMed 15262912McEniery CM, Schmitt M, Qasem A, Webb DJ, Avolio AP, Wilkinson IB, Cockcroft JR. Nebivolol increases arterial distensibility in vivo. Hypertension. 2004 Sep;44(3):305-10. doi: 10.1161/01.HYP.0000137983.45556.6e. Epub 2004 Jul 19.
- Background: PubMed 1593914Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
- Background: PubMed 16296572Van Bortel LM, Bulpitt CJ, Fici F. Quality of life and antihypertensive effect with nebivolol and losartan. Am J Hypertens. 2005 Aug;18(8):1060-6. doi: 10.1016/j.amjhyper.2005.03.733.
- Background: PubMed 9990650Mangrella M, Rossi F, Fici F, Rossi F. Pharmacology of nebivolol. Pharmacol Res. 1998 Dec;38(6):419-31. doi: 10.1006/phrs.1998.0387.
- Background: PubMed 2773795Roman MJ, Devereux RB, Kramer-Fox R, O'Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol. 1989 Sep 1;64(8):507-12. doi: 10.1016/0002-9149(89)90430-x.
- Results publication: PubMed 16601194Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006 Apr 7;312(5770):117-21. doi: 10.1126/science.1124287.
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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.
Eloisa Arbustini, MD,FESC,FACC principal investigator
IRCCS Foundation San Matteo Hospital, Pavia
Luigi Tavazzi, MD,FESC,FACC study chair
IRCCS Foundation San Matteo Hospital, Pavia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Losartan and nebivolol, Losartan and Nebivolol in people with Marfan Syndrome, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
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 3 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 22 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eloisa Arbustini, MD,FESC,FACC (+390382501206, e.arbustini@smatteo.pv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BSA and age-adjusted aortic root diameter (sinuses of Valsalva) (time frame: every 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00683124, which also lists 15 linked publications.
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 22 Jul 2011.