Advancing understanding of treatment through clinical trials

November 4, 2012, American Society of Nephrology

Three late-breaking studies presented during the American Society of Nephrology's Annual Kidney Week provide new information on drugs being tested in patients with diabetes or kidney disease.

Hans-Henrik Parving, MD (University of Copenhagen, in Denmark) and his colleagues investigated whether the drug aliskiren might improve the prognosis of with who are at high risk for developing heart and kidney problems. The randomized double-blind ALTITUDE trial included 8561 individuals who received aliskiren (300 mg once daily) or placebo on top of a drug that blocks the renin-angiotensin-aldosterone system (RAAS), a complex that regulates blood pressure and fluid balance. (Drugs that target the RAAS have limited effectiveness in part due to feedback responses, such as compensatory increases in an enzyme called renin. Aliskiren is a direct renin inhibitor and may help overcome these shortcomings because it suppresses the reactive rise in renin activity stimulated by other RAAS blockers.) After an average follow-up of 32.9 months:

  • 17.9% of patients receiving aliskiren and 16.8% of those receiving placebo experienced a heart attack or stroke, developed , or died of cardiovascular disease.
  • Stroke occurred in 3.4% of patients taking aliskiren, compared with 2.7% of patients taking placebo.
  • Patients taking aliskiren experienced significantly increased and hypotension.
"The trial does not support administration of aliskiren on top of standard therapy with RAAS blockade in type 2 diabetic patients at high risk for cardiovascular and renal events, and may even be harmful," the authors concluded.

Another team led by Vicente Torres, MD, PhD (Mayo Clinic) tested the potential of a vasopressin V2 (tolvaptan) to inhibit cyst growth and slow decline in patients with autosomal dominant (ADPKD). This condition causes kidney cysts often associated with pain, hypertension, and kidney failure. The phase 3, multi-center, double-blind, placebo-controlled, 3-year trial included 1445 ADPKD patients who were randomized 2:1 to split dose tolvaptan (45/15, 60/30 or 90/30 mg daily as tolerated) or placebo.

  • Total kidney volume increase over 3 years was halved in patients treated with tolvaptan compared to placebo (2.80%/year versus 5.51%/year).
  • Patients taking tolvaptan were 61% less likely to experience a certain level of worsening kidney function and 36% less likely to experience kidney pain requiring treatment.
  • Tolvaptan slowed the rate of kidney function decline compared with placebo.
"Tolvaptan demonstrated clinically meaningful disease-specific benefits for ADPKD patients which may be clinically meaningful," said Dr. Torres. While the trial findings are encouraging, tolvaptan has not yet been approved for this indication.

A third trial, called EVOLVE, was designed to test the hypothesis that treatment with cinacalcet compared with placebo reduces the risk of premature death or non-fatal heart-related events among dialysis patients with secondary hyperparathyroidism. (Secondary hyperparathyroidism, when the parathyroid gland produces excess amounts of parathyroid hormone, arises in most patients with chronic disease as their disease progresses. It can lead to a number of complications, including cardiovascular problems.) Results from analyses using multivariable adjustment and censoring data 6 months after patients stopped taking the drug will be presented, along with safety data, by Glenn Chertow, MD (Stanford University School of Medicine).

Explore further: Median follow-up results from the ALTITUDE study

More information: Study co-authors for "The Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)" (abstract 6313) include Barry M. Brenner, MD, John Mcmurray, Dick de Zeeuw, MD, PhD, Steven Mark Haffner, MD, Scott D. Solomon, MD, Nish Chaturvedi, Frederik I. Persson, MD, Akshay Suvas Desai, Maria Nicolaides, and Marc A. Pfeffer, MD, PhD.

Study co-authors for "Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: The TEMPO 3:4 Trial" (abstract 6357) include Arlene B. Chapman, MD, Olivier Devuyst, MD, PhD, Ron T. Gansevoort, MD, PhD, Jared J. Grantham, MD, Eiji Higashihara, MD, Ronald D. Perrone, MD, Holly B. Krasa, John Ouyang, PhD, Osamu Sato, and Frank S. Czerwiec, MD, PhD.

Study co-authors for "Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial" (abstract 6450) include Geoffrey A. Block, MD, Ricardo Correa-Rotter, MD, Tilman B. Drueke, MD, Jurgen Floege, MD, William G. Goodman, MD, Christian Mix, MD, Marie-Louise Trotman, Yumi Kubo, Charles A. Herzog, MD, Gerard M. London, MD, Kenneth Mahaffey, MD, Sharon M. Moe, MD, David C. Wheeler, MD, and Patrick S. Parfrey, MD.

Related Stories

Median follow-up results from the ALTITUDE study

August 27, 2012
Preliminary results from the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) do not support administration of aliskiren on top of standard therapy with renin-angiotensin-aldosterone system (RAAS) ...

Vitamin B derivative helps diabetics with mild kidney disease

October 27, 2011
A vitamin B6 derivative may help slow or prevent the progression of mild kidney disease in patients with diabetes, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). ...

Promising kidney drug fails in large clinical trial

October 27, 2011
What was hoped to be a promising new drug to protect the kidneys has failed to benefit diabetes patients with kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology ...

Study questions safety and effectiveness of common kidney disease drugs

July 19, 2012
Drugs commonly prescribed to patients with chronic kidney disease (CKD) may not be as strongly effective as once thought, and may cause unexpected harm to blood vessels, according to a study appearing in an upcoming issue ...

Recommended for you

New study validates clotting risk factors in chronic kidney disease

January 17, 2018
In late 2017, researchers from Boston University School of Medicine (BUSM) discovered and published (Science Translational Medicine, (9) 417, Nov 2017) a potential treatment target to prevent chronic kidney disease (CKD) ...

Newly-discovered TB blood signal provides early warning for at-risk patients

January 17, 2018
Tuberculosis can be detected in people with HIV infection via a unique blood signal before symptoms appear, according to a new study by researchers from the Crick, Imperial College London and the University of Cape Town.

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

Fresh approach to tuberculosis vaccine offers better protection

January 17, 2018
A unique platform that resulted in a promising HIV vaccine has also led to a new, highly effective vaccine against tuberculosis that is moving toward testing in humans.

New study offers insights on genetic indicators of COPD risk

January 16, 2018
Researchers have discovered that genetic variations in the anatomy of the lungs could serve as indicators to help identify people who have low, but stable, lung function early in life, and those who are particularly at risk ...

Previous influenza virus exposures enhance susceptibility in another influenza pandemic

January 16, 2018
While past exposure to influenza A viruses often builds immunity to similar, and sometimes different, strains of the virus, Canadian researchers are calling for more attention to exceptions to that rule.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.