Woman's death during drug trial questioned

By Martin Johnston

Photo / File
Photo / File

The Solicitor-General is considering whether to re-open a coroner's examination of the death of a woman while she was on a clinical trial of a controversial drug.

Medicines importer Lance Gravatt, who supplies a rival drug, petitioned Solicitor-General Mike Heron QC to hold an inquest and raised questions about the trial medicine, benzbromarone, used to treat gout.

Read more
Gout no worse for the obese - study

Benzbromarone was withdrawn in Europe in 2003 because of liver toxicity. The 47-year-old Cook Island Maori woman's death was linked to liver disease.

Chief coroner Judge Neil MacLean told Dr Gravatt there appeared to be no reference in coronial files to the woman having been on a clinical trial.

The files list benzbromarone as one of her 13 medicines, but under a different name.

Dr Gravatt, an organic chemist, said: "Had the coroner been aware that this woman was involved in a clinical trial with a hepatotoxic experimental drug ... the proper course would have been to open an investigation."

The drug is not licensed by Medsafe, meaning it is prescribed "off-label", putting greater onus on doctors to explain its risks and benefits. Medsafe last year warned doctors of its interaction with the blood anti-clotting medicine warfarin.

Judge MacLean released the woman's autopsy report to Dr Gravatt but withheld her name to avoid aggravating her family's grief.

The report says the cause of death was: "Chronic renal disease secondary to gout in association with cirrhosis of the liver". Just before death, "she developed bleeding from one of the ulcers [on her feet] and then collapsed."

A 2005 NZ Medical Journal paper on the Middlemore Hospital trial involving six patients with severe gout says the woman died from "severe blood loss" from an ulcerated gout lump.

"Her autopsy showed she had liver cirrhosis, which had not been diagnosed previously. She died from complication of gout, and benzbromarone was not thought to have contributed towards her death."

The trial's rules were to exclude patients with abnormal results on liver function tests, which were conducted at recruitment and then monthly.

"All patients tolerated benzbromarone well; no patients experienced major side effects. Liver function tests remained normal in all patients ... "

Middlemore said it would be improper to answer questions on the trial while the matter was before the Solicitor-General.

A doctor, who asked not to be named, told the Herald the statements on cause of death by the autopsy pathologist and the researchers were not in conflict. The blood loss was an acute event, while the organ disease and gout were the underlying, chronic disorders.

But it would be unusual - although possible - for liver abnormalities not to have shown up in liver tests in a person in whom liver damage was discovered after death.

Dr Gravatt, whose son died of meningococcal disease after failings in his care, said he took up the woman's case as she too might have suffered treatment injury and her estate might be entitled to accident compensation cover.

He said liver disease could be misdiagnosed as recurrent urinary tract infections and the woman was recorded as having the latter. She might have been wrongly enrolled in the trial, and benzbromarone might have contributed to her death. Pharmac's decision to fund the drug might have been based on erroneous data about its safety.

Dr Gravatt has asked Medsafe to initiate an import ban on benzbromarone. The authority's group manager, Dr Stewart Jessamine, said it would refer the matter to the Centre for Adverse Reactions Monitoring to investigate if there was a causal link between the drug and the effects on the woman.

What is gout?

• A form of arthritis
• Swollen, painful joints, especially the big toes
• Caused by excess uric acid, which crystallises in joints and tissues
• Risk factors include family history of the disease, high blood pressure, excess alcohol intake
• More common in men
• Estimated to affect 14% of Maori men and 6% of Pakeha men

- NZ Herald

© Copyright 2014, APN New Zealand Limited

Assembled by: (static) on production bpcf04 at 19 Dec 2014 10:54:02 Processing Time: 415ms