Clinical trial NCT00097786: Long-term Study of Nateglinide+Valsartan to Prevent or Delay Type II Diabetes Mellitus and Cardiovascular Complications
Official title: A Multinational, Randomized, Double-blind, Placebo-controlled, Forced-titration, 2 x 2 Factorial Design Study of the Efficacy and Safety of Long-term Administration of Nateglinide and Valsartan in the Prevention of Diabetes and Cardiovascular Outcomes in Subjects With Impaired Glucose Tolerance (IGT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Prevention
Diabetes type 2
valsartan
nateglinide
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2004-12-01
Enrollment: 9306
Sex: ALL
Minimum age (years): 50
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: This study is a test of the safety and effectiveness of two drugs, one for diabetes and one for hypertension, in keeping patients with high lab values of glucose from progressing to frank diabetes and developing cardiovascular complications. People in this study cannot have frank diabetes but are considered "borderline" based on blood tests. People in the study take none, one or both of the drugs and do not know which one(s) they are taking.


Eligibility criteria: Inclusion Criteria:

* Adults
* Impaired glucose tolerance
* Age dependent risk factors

Exclusion Criteria:

* Frank diabetes

For detailed information, call contact person.

Primary outcomes:
measure: Percentage of Patients Reaching the Endpoint: Progression to Diabetes - Valsartan Versus Non-valsartan
timeFrame: Mean patient duration of 4.2 years
measure: Percentage of Patients Reaching the Endpoint: Extended Morbidity and Mortality Event - Valsartan Versus Non-valsartan
timeFrame: Mean patient duration of 5.6 years
measure: Percentage of Patients Reaching the Endpoint: Core Cardiovascular Morbidity and Mortality Event - Valsartan Versus Non-valsartan
timeFrame: Mean patient duration of 5.8 years
measure: Percentage of Patients Reaching the Endpoint: Progression to Diabetes - Nateglinide Versus Non-nateglinide
timeFrame: Mean patient duration of 4.2 years
measure: Percentage of Patients Reaching the Endpoint: Extended Morbidity and Mortality Event - Nateglinide Versus Non-nateglinide
timeFrame: Mean patient duration of 5.6 years
measure: Percentage of Patients Reaching the Endpoint: Core Cardiovascular Morbidity and Mortality Event - Nateglinide Versus Non-nateglinide
timeFrame: Mean patient duration of 5.8 years
Secondary outcomes:
Other outcomes:
Locations:
city: Multiple Locations
country: United States
state: New Jersey
city: Investigative Site
country: Argentina
city: Investigative Site
country: Australia
city: Multiple Locations
country: Austria
city: Investigative Site
country: Belgium
city: Investigative Site
country: Brazil
city: Investigative Site
country: Canada
city: Investigative Site
country: Chile
city: Investigative Site
country: China
city: Investigative Site
country: Colombia
city: Investigative Site
country: Czechia
city: Investigative Site
country: Denmark
city: Investigative Site
country: Ecuador
city: Investigative Site
country: Finland
city: Investigative Site
country: France
city: Investigative Site
country: Germany
city: Investigative Site
country: Greece
city: Investigative Site
country: Guatemala
city: Investigative Site
country: Hong Kong
city: Investigative Site
country: Hungary
city: Investigative Site
country: Italy
city: Investigative Site
country: Malaysia
city: Investigative Site
country: Mexico
city: Investigative Site
country: Netherlands
city: Investigative Site
country: Norway
city: Investigative Site
country: Peru
city: Investigative Site
country: Poland
city: Investigative Site
country: Russian Federation
city: Investigative Site
country: Singapore
city: Investigative Site
country: Slovakia
city: Investigative Site
country: South Africa
city: Investigative Site
country: Spain
city: Investigative Site
country: Sweden
city: Investigative Site
country: Switzerland
city: Investigative Site
country: Taiwan
city: Investigative Site
country: Turkey
city: Investigative Site
country: United Kingdom
city: Investigative Site
country: Uruguay
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Harumi Higuchi Dos Santos M, Sharma A, Sun JL, Pieper K, McMurray JJ, Holman RR, Lopes RD. International Variation in Outcomes Among People with Cardiovascular Disease or Cardiovascular Risk Factors and Impaired Glucose Tolerance: Insights from the NAVIGATOR Trial. J Am Heart Assoc. 2017 Jan 13;6(1):e003892. doi: 10.1161/JAHA.116.003892.
citation: Preiss D, Thomas LE, Wojdyla DM, Haffner SM, Gill JM, Yates T, Davies MJ, Holman RR, McMurray JJ, Califf RM, Kraus WE; NAVIGATOR Investigators. Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study. BMJ Open. 2015 Aug 14;5(8):e007901. doi: 10.1136/bmjopen-2015-007901.
citation: Katz M, Califf RM, Sun JL, McMurray JJ, Thomas L, Lopes RD. Venous thromboembolism and cardiovascular risk: results from the NAVIGATOR trial. Am J Med. 2015 Mar;128(3):297-302. doi: 10.1016/j.amjmed.2014.08.022. Epub 2014 Nov 20.
citation: Preiss D, Haffner SM, Thomas LE, Sun JL, Sattar N, Yates T, J Davies M, McMurray JJ, Holman RR, Califf RM, Kraus WE. Change in levels of physical activity after diagnosis of type 2 diabetes: an observational analysis from the NAVIGATOR study. Diabetes Obes Metab. 2014 Dec;16(12):1265-8. doi: 10.1111/dom.12320. Epub 2014 Jun 19.
citation: Huffman KM, Sun JL, Thomas L, Bales CW, Califf RM, Yates T, Davies MJ, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Haffner SM, Kraus WE. Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: results from NAVIGATOR. Metabolism. 2014 Apr;63(4):554-61. doi: 10.1016/j.metabol.2014.01.002. Epub 2014 Jan 15.
citation: Yates T, Haffner SM, Schulte PJ, Thomas L, Huffman KM, Bales CW, Califf RM, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Davies MJ, Kraus WE. Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis. Lancet. 2014 Mar 22;383(9922):1059-66. doi: 10.1016/S0140-6736(13)62061-9. Epub 2013 Dec 20.
citation: Shen L, Shah BR, Reyes EM, Thomas L, Wojdyla D, Diem P, Leiter LA, Charbonnel B, Mareev V, Horton ES, Haffner SM, Soska V, Holman R, Bethel MA, Schaper F, Sun JL, McMurray JJ, Califf RM, Krum H. Role of diuretics, beta blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013 Dec 9;347:f6745. doi: 10.1136/bmj.f6745.
citation: NAVIGATOR Study Group; McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar J, Califf RM. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010 Apr 22;362(16):1477-90. doi: 10.1056/NEJMoa1001121. Epub 2010 Mar 14.
citation: NAVIGATOR Study Group; Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar J, Califf RM. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010 Apr 22;362(16):1463-76. doi: 10.1056/NEJMoa1001122. Epub 2010 Mar 14.
citation: Krum H, McMurray JJ, Horton E, Gerlock T, Holzhauer B, Zuurman L, Haffner SM, Bethel MA, Holman RR, Califf RM. Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. Cardiovasc Ther. 2010 Apr;28(2):124-32. doi: 10.1111/j.1755-5922.2010.00146.x. Epub 2010 Feb 23.
citation: Bethel MA, Deedwania P, Levitt NS, Schmitz O, Huntsman-Labed A, Califf RM, Haffner SM, Diem P; NAVIGATOR Study Group. Metabolic syndrome and alanine aminotransferase: a global perspective from the NAVIGATOR screening population. Diabet Med. 2009 Dec;26(12):1204-11. doi: 10.1111/j.1464-5491.2009.02864.x.
citation: Bethel MA, Holman R, Haffner SM, Califf RM, Huntsman-Labed A, Hua TA, McMurray J. Determining the most appropriate components for a composite clinical trial outcome. Am Heart J. 2008 Oct;156(4):633-40. doi: 10.1016/j.ahj.2008.05.018. Epub 2008 Jul 31.