Children to get Viagra in lung disease trial

Viagra is being given to babies and children around the world to try to save them from life-threatening lung conditions. The anecdotal evidence and case studies reported so far suggest the anti-impotence drug is a promising treatment for pulmonary hypertension (PHT) in both children and adults.

Nonetheless, some critics have expressed serious concern at the fact that no clinical trials have taken place for this use of the drug and at the wide variation in doses used.

But New Scientist has learned that multicentre clinical trials on adults are already enrolling patients and that trials on children will start in the next few months.

The latest use of Viagra in babies was in India, where P K Rajiv, a neonatologist at Amrita Institute of Medical Sciences in Kochi, used sildenafil citrate (the chemical name for Viagra) to treat three newborn babies.

"It was a life-threatening situation and as a doctor it is my duty to save the child with whatever is at my disposal," Rajiv said. But the controversy following the revelation led Rajiv to say he will not use the drug again until the Indian regulatory authorities sanction a clinical study.

Wrong impression

Medical ethicists are sympathetic but point out the dangers. "There are circumstances in which it is morally justifiable to try new treatments when there is an impression that a drug may save a life. But the danger of doing so without a clinical trial is that your impression may be wrong," says Raanan Gillon, emeritus professor of medical ethics at Imperial College London.

David Wessel, director of the cardiology unit at Boston Children's Hospital is also critical, saying it is premature to use the drug since there have been no published randomised trials in children. "I could not recommend the use of sildenafil outside the context of a properly designed clinical trial," he told New Scientist.

However, Wessel is one of a number of clinicians who have already given Viagra to patients as young as six weeks old. He says this was done in accordance with the hospital's code of ethics and with the parents' consent. Since 1998 he has prescribed the drug for 14 children with PHT, some of whom later died due to their condition.

Ian Adatia, director of the Pulmonary Hypertension Clinic at Toronto's Hospital for Sick Children, told New Scientist he has given the drug to 10 children, with encouraging results.

"At the moment it is given on a compassionate use basis agreed with the hospital's ethics board," he says. "But we will be involved in the multicentre trials with Pfizer using intravenous sildenafil." Doctors have pushed for an intravenous form of Viagra, as they believe it may lead to better results than the current oral form.

Making sense

The treatment has also been tried at the Royal Brompton Hospital in London, UK, where Alan Magee told New Scientist he has treated five children, all of whom "reported significant improvement in well being and exercise capacity".

Pfizer, the company that created Viagra, confirm they are funding the adult trial but will only say they "hope" to pursue clinical trials in children. "It's pretty rare that we even talk at this stage of research," says spokesman Jeff Cook.

He says it makes sense that the drug shows promise in treating PHT, given that the original purpose of Viagra was to treat angina by opening up blood vessels. "From a mechanistic standpoint it makes a lot of sense," he says.

Blue babies

There are two types of PHT - both potentially fatal. Primary PHT is a debilitating condition of unknown cause. It affects 28,000 children and 250,000 adults in the US alone and is often fatal without a lung transplant

Persistent PHT afflicts babies in whom the transition from foetal circulation, which bypasses the lungs, to postnatal circulation does not occur properly. The bypass vessel fails to close after birth, the baby soon turns blue from lack of oxygen and is at risk of dying from heart failure.

The standard treatment is to put the baby on a ventilator and then administer nitric oxide by inhalation (iNO). Nitric oxide is produced naturally by the body and works by raising the blood levels of a vasodilator called cGMP (cyclic guanosine-monophosphate).

Rajiv prescribed sildenafil for an eight-hour-old baby girl with the disorder, after the inhalation treatment failed. "The child recovered in 48 hours and within a week two other newborns survived the same treatment," he said.

Targeted treatment

Rajiv had read about the treatment in a study published in the journal Circulation, which compared 13 adults with primary PHT who were treated with iNO or Viagra.

Evangelos Michelakis, the cardiologist who carried out that study at the University of Alberta in Canada, says that Viagra appears to work better than iNO and have fewer side-effects. "Viagra works in two ways: it is a vasodilator and it also inhibits the enzyme that breaks down cGMP, so its effect is longer lasting.

Magee adds that the enzyme is mostly found in the lung and the penis, with little elsewhere in the body. This means it should not cause a general lowering of blood pressure. "This is also our experience," he says.

Primary PHT patients must be constantly attached to a ventilator or an intravenous line supplying prostocyclin, a vasodilator. But Viagra could allow patients to be weaned off these treatments. There may also be significant cost advantages to using Viagra to treat PHT, especially in developing countries, as it is cheaper than ventilation.

However, Michelakis is unhappy with the drug's widespread use in newborns. "It is dangerous because doctors cannot know what dosage to give, how long to give it and what the long-term effects might be," he told New Scientist.

Off licence

The use of Viagra to treat PHT in babies and children, despite the lack of clinical trials, highlights a much wider issue. It is estimated that 90 per cent of all drugs used on newborns and half the drugs prescribed for children were only licensed for adults, or for other illnesses.

"The problem is paediatric medicine is not a viable market for pharmaceutical companies to invest in because there are far more adults than children with a particular condition," says Richard Nicholson, editor of the Bulletin of Medical Ethics.

But Pfizer's Jeff Cook says: "As company committed to developing medicine to help patients we recognise that not all indications are going to be hugely successful from a financial standpoint."

A European Union directive still in consultation is expected to offer a six month patent extension to drugs that have been tested on children.

Gaia Vince and Damian Carrington

This story is from NewScientist.com's news service - for more exclusive news and expert analysis every week subscribe to New Scientist print edition.

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