REPRISE study confirms tolvaptan efficacy

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The first clinical trial of Tolvaptan showed that it was effective in slowing the growth of the total kidney volume (TKV*) and in slowing the decline in eGFR* in ADPKD patients. However, that trial focussed on patients in the early stages of their disease process. Now there is evidence that Tolvaptan also works in patients at the later stages of ADPKD.


Results of a second trial called ‘REPRISE’ were announced in November 2017. In this trial, patients started taking Tolvaptan and then, after a period, were randomly selected to take either a placebo in its place or to continue with Tolvaptan.
This type of trial is called a ‘placebo-controlled, double-blind trial’. Neither doctors nor patients knew whether they were taking the active drug or the placebo which avoids bias. For each patient who continued to receive Tolvaptan there was one who was on the placebo. They continued with the treatment for 12 months. The study was carried out in several centres across US, UK and Europe.

The patients in REPRISE were between 18 and 65 years old and results were analysed in two groups (18–55yrs and 56–65yrs).

The younger group had an eGFR from 65 down to 25 (ml/minute/1.73 m2).

The older group had an eGFR from 44 to 25. The important end point measurement was the change in eGFR from the baseline at the start of the trial to the end of the trial.

For those patients taking Tolvaptan the drop in eGFR was significantly smaller than for those patients on the placebo.

Over the year the controls, or placebo group, had an average drop in eGFR of 3.61 ml/minute/1.73 m2, while in the Tolvaptan group the drop was 2.34 ml/minute/1.73 m2. This difference is statistically significant.

From the safety aspect a few patients had slight rises in liver enzymes, but they returned to normal on stopping Tolvaptan. Indeed some of the people in the placebo group also had rises.

The conclusion from this trial is that Tolvaptan results in a slower decline in the eGFR for patients in the later stages of the disease process. So it is effective even for patients who already have a reduced eGFR, as low as 25.

It may take a while for the study results to be implemented into clinical practice and currently Tolvaptan is limited in its licence to certain patients with higher eGFR. This is however certainly good news for all ADPKD patients.

Explanation of terms:

* Total Kidney Volume (TKV) is calculated from measurements made at an MRI scan and is known to relate to kidney function. As the TKV increases so the function falls, or larger kidneys tend to have lower function.

* Estimated glomerular filtration rate (eGFR) is calculated from measurements of the creatinine in the blood and it is an approximation of how well the kidneys are working – a low eGFR equates to a low kidney function. It is measured in units ml/minute/1.73 m2.

Vasopressin is a hormone that causes cyst cells to increase in number and to secrete more fluid into the cyst. It does this through a messenger called cAMP.

Tolvaptan is a drug that blocks the actions of vasopressin.

Link to the paper.

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