Clinical trials are used to determine the efficacy of a drug in patients. However, effective clinical trials that have a large sample size and are double-blind and controlled, are expensive and lengthy. Research suggests that the median cost of a trial is $19 million and can take six to seven years to complete.
A solution may come from supplementing clinical trial data with real-world evidence. This is especially prudent in cases where few trials have been done or cannot be done. A retrospective cohort study aimed to supplement clinical trial data by carrying out a real-world study on migraine sufferers and candesartan. The study included different headache types and monitored the effects of the drug over a long time period.
Migraines – not just a Headache
Migraines are classified as either Episodic (EM) or Chronic (CM). They are moderate to severe headaches usually affecting one side of the head, which are frequently accompanied by feeling sick and increased sensitivity to light. The exact causes of migraines are unknown, although there is evidence of a genetic component to familial hemiplegic migraines. However, most seem to be due to various dietary, emotional and environmental triggers. Migraines can be debilitating, affecting 1 in 5 women and 1 in 15 men, and can last for hours or even days. At present, there is no cure for migraines, but possible treatments for the condition are being investigated.
Candesartan is an angiotensin II receptor blocker (ARB), originally used for arterial hypertension but it has since been explored in the treatment of headaches. However, the use of candesartan for the treatment of headaches has only been investigated in two clinical trials to date. Currently, candesartan is recommended for use across America and Europe. However, it is not commonly used in Spain potentially due to the lack of evidence for CM and treatment-resistant patients.
This study identified a lack of real-world evidence for the use of Candesartan for migraine sufferers. Therefore, they undertook an analytic observational study, with a retrospective cohort design, to properly evaluate the effectiveness and tolerability of the drug for migraine treatment.
The RWE trial for Candesartan
Using the Headache Unit of Hospital Clínico Universitario de Valladolid, the study identified 120 suitable participants. This was from a reference population of 280,000 patients, and by reviewing medical records from April 2008 to February 2019.
The two previous clinical trials were of modest size. They included a majority of EM patients and did not address concerns of adverse effects, or those suffering from medication-overuse headaches (MOH). By examining the medical records, the team hoped to answer these questions.
This study included 100 women, and the majority of the participants were chronic migraine sufferers. 42.7% fulfilled the MOH criteria.
Summary of Results
Before candesartan use, the mean number of headaches per month was 20.5. This reduced to 16.2 after 8-12 weeks, then further to 15.6 after 20-24 weeks. Adverse side-effects caused 18.3% to discontinue the trial, citing light-headedness, hypotension, sleepiness or other unspecified effects.
Overall, candesartan resulted in a significant decrease in headaches per month in treatment-resistant, chronic and episodic sufferers. The study also reported on the drug’s efficacy up to and after 6 months. This is the first time this has been assessed, despite the guidelines recommending staying on candesartan for at least 6 months.
Sadly, no magic bullet drug exists for migraines, but combining small clinical trials with large observational cohorts allows for better characterisation of the effectiveness and tolerability of drugs in a real-world context.