Uloric clinical trials were postmarket medical studies done on the gout medication, Uloric, after it had been approved by the U.S. Food and Drug Administration (FDA). These trials found side effects of Uloric included a higher risk of a patient developing a fatal heart condition than other gout medications. At the conclusion of the trials, the FDA issued a warning to people taking Uloric of these risks of a major cardiovascular event, and updated the warning label on the drug.
- 1. Clinical trial reveals increased risk of cardiovascular problems from taking Uloric
- 2. FDA issues safety announcement and updates Uloric’s warning label
- 3. Warnings come too late for many Uloric users
1. Clinical trial reveals increased risk of cardiovascular problems from taking Uloric
After Uloric was approved, a postmarket trial was conducted by the U.S. manufacturer of the drug, Takeda Pharmaceutical, to track whether the drug threatened patients’ hearts. That trial found that Uloric’s side effects included a higher risk of causing death, including heart-related death, than other medications for gout.
When the FDA approved Uloric for medical use in the U.S. in 2009, the agency was concerned about the risks that the drug posed for cardiovascular problems. The FDA was so concerned that it only approved the 40 milligram and 80 milligram doses of Uloric, rather than Takeda’s requested approval for doses of 80 milligrams and 120 milligrams of the drug.1
The FDA also included a warning on Uloric’s label that mentioned the increased risk for serious cardiovascular problems,2 and mandated a postmarket clinical trial as a part of Uloric’s approval.3
That postmarket clinical trial was supposed to begin on January 31, 2010, end four years later, and be submitted to the FDA on January 31, 2015.4 The trial, which was randomized and double-blind, was to track thousands of people with gout who were either prescribed Uloric or the older gout prescription, Zyloprim. The trial was to last for several years and monitor the participants for cardiovascular events like:
- Heart-related death,
- Stroke,
- Heart attack, and
- Unstable angina, a medical condition involving a diminished blood flow to the heart.
There was no placebo, or control group, in the trial.
The results of the postmarket trial, called the CARES trial, were first released on June 14, 2018.5
The trial followed 6,198 people in the U.S., Canada, and Mexico who suffered from gout. Half of the participants in the study took Uloric for their gout. The other half took the older drug, Zyloprim. The trial followed their progress for seven years, from April 23, 2010 until July 18, 2017. More than half of the trial’s participants, 3,410 of them, completed the trial. Of the participants who completed the trial, 1,704 had taken Uloric, while 1,706 had taken Zyloprim.
The results were mixed:
| Uloric (3,098 (100%)) | Zyloprim (3,092 (100%)) | |
| Cardiovascular death | 134 (4.3%) | 100 (3.2%) |
| Nonfatal Heart Attack | 111 (3.6) | 118 (3.8) |
| Nonfatal Stroke | 71 (2.3) | 70 (2.3) |
| Nonfatal Unstable Angina | 49 (1.6) | 56 (1.8) |
| Total deaths | 243 (7.8) | 199 (6.4) |
While the CARES trial found that there was little difference in the number of people on Uloric or Zyloprim who had a heart attack, stroke, or unstable angina, it found a significantly increased risk for cardiovascular death or death by other causes.6
2. FDA issues safety announcement and updates Uloric’s warning label
In the aftermath of the CARES trial, the FDA issued a safety announcement for Uloric users and updated the warning label for the drug.
The safety announcement warned people that Uloric came with an increased risk of death over Zyloprim, the other long-term gout prescription on the market.7 The safety announcement also narrowed the FDA’s approved use of Uloric to patients who already tried Zyloprim, but who either experienced side effects or had limited success with the older drug. It also told patients to look out for problematic symptoms of Uloric, including:
- Chest pain,
- Shortness of breath or difficulty breathing,
- Dizziness,
- A sudden and severe headache,
- Difficulty talking,
- A rapid or irregular heartbeat, or
- Numbness or weakness on only one side of the body.
The updated warning label for Uloric included a new boxed warning for cardiovascular death.8
3. Warnings come too late for many Uloric users
The FDA’s warnings after the CARES trial, though, do not help people who have taken Uloric as a treatment for their gout since it was first approved by the FDA in 2009. These patients have been unknowingly dealing with an increased risk of a potentially fatal heart problem for years.
If you suspect that your heart problems are associated with your use of Uloric, you may have legal options. There are Uloric mass tort lawsuits against Takeda Pharmaceutical for the potentially fatal side effects caused by Uloric. These lawsuits aim to recover the compensation that victims need and deserve after suffering from a cardiovascular event caused by the drug.
Legal References:
- FDA Approval Letter for Uloric – 2009.
- FDA Warning Label for Uloric – 2009.
- See note 1.
- See note 1.
- Cardiovascular Safety of Febuxostat and Allopurinol in Participants With Gout and Cardiovascular Comorbidities.
- See Choi H, Neogi T, Stamp L, Dalbeth N, Terkeltaub R, “New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert,” Arthritis Rheumatology 70(11):1702-9 (November 2018).
- FDA Drug Safety Communication, “FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat),” (February 21, 2019).
- FDA Warning Label for Uloric – 2019.