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Case study: Interact 2 Impact Case Study

The evidence from the study changed acute intracerebral haemorrhage guidelines in the UK and across Europe, the United States and Australia.

Find out more

INTERACT 2 Impact case Study

INTERACT2

Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial 2

 

Key features

  • October 2008 - August 2013
  • An international, multicentre study, with several UK sites involved
  • Leicester Cardiovascular Biomedical Research Unit was the UK hub
  • UK Chief Investigator: Professor Tom Robinson, NIHR Clinical Research Network National Specialty Lead for Stroke
  • 70 participants recruited in the UK
  • NIHR provided dedicated research nurses and infrastructure support

Acute intracerebral haemorrhage, which is the least treatable form of stroke, affects more than one million people worldwide annually. This is when blood suddenly bursts into brain tissue, causing damage to the brain. Blood pressure often becomes elevated after intracerebral haemorrhage, frequently reaching very high levels. Because of this there is an increased chance of disability and death, and there are limited therapeutic options for this form of stroke.

Following the results of the pilot phase study, Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial 1 (INTERACT1), the main phase study was conducted, INTERACT2. The aim of the study was to determine the safety and effectiveness of early intensive lowering of blood pressure in patients with intracerebral haemorrhage, and whether it would improve patient outcomes.

INTERACT2 was an international, multicentre, prospective, randomized, open-treatment, blinded end-point trial.

The study compared the effect of an intensive (<140mmHg systolic blood pressure) versus the current guideline (<180) strategy of lowering blood pressure within six hours of spontaneous intracerebral haemorrhage onset in patients with baseline systolic blood pressure between 150 and 220mmHg.

The drug used and how it was administered, in both study groups, was decided by the clinician leading each patient’s treatment. This was to make sure treatment was timely and safe, complied with local guidelines, and therefore the results were more likely to be generalisable.

The primary outcome was death or major disability at 90 days. The rate of serious adverse events was also compared between the two groups.

From October 2008 to August 2012, a total of 2839 participants were enrolled at 144 hospitals in 21 countries; 1403 participants were randomly assigned to receive early intensive treatment to lower their blood pressure, and 1436 were assigned to receive guideline-recommended treatment. Written informed consent was obtained from each patient or their family.

The study was led internationally by the George Institute for Global Health in Australia and funded by the National Health and Medical Research Council of Australia.

There were several sites in the UK involved in the delivery of the study, with Leicester Cardiovascular Biomedical Research Unit the hub. The study was delivered to time and target.

The study was on the NIHR Clinical Research Network’s Portfolio and received NIHR infrastructure support, including research nurses, to deliver the study.

Outcomes and findings

The study found that early intensive lowering of blood pressure, compared with the recommended guidelines, did not result in a significant reduction in the rate of the primary outcome of death or major disability.

However, the study did find there were significantly better functional outcomes among patients assigned to intensive treatment to lower their blood pressure than among patients assigned to guideline-recommended treatment. At 90 days, 719 of the participants (52.0%) in the intensive-treatment group, compared with 785 (55.6%) in the standard-treatment group, had a poor outcome.

There was also significantly better physical and psychological well-being among patients who received intensive treatment. Participants in the intensive treatment group reported fewer problems and had significantly better overall health related quality of life at 90 days than did those in the standard treatment group.

The results indicate that early intensive lowering of blood pressure in these patients is safe.

The rate of death from any cause was similar in the intensive-treatment group and the standard-treatment group (11.9% and 12.0%, respectively), as was the percentage of these deaths attributed to the direct effect of the intracerebral haemorrhage. Also the number of serious adverse events, including episodes of severe hypotension (which occurred in <1% of the participants), were also balanced between the two groups.

It was also found that intravenous (e.g. injection or drip) administering of the chosen agents was faster acting than when it was given orally.

The range of drug therapies used and participant outcomes assessed from a variety of hospitals in different countries enhances the generalisability of the final results. This means the findings could be more easily implementable internationally.

Value to the NHS

The evidence from the INTERACT2 study has changed acute intracerebral haemorrhage guidelines in the UK, and across Europe, United States of America and Australia.

In the UK, most NHS hospitals now have an intensive blood pressure lowering protocol.

Also since the study was published in June 2013, a further award to support a NIHR and British Association of Stroke Physicians writing group has been granted to develop a funding application to undertake an implementation study of best treatment for the management of intracerebral haemorrhage, which includes an intensive blood pressure lowering protocol.

This is a real chance for us to improve treatment of this devastating form of stroke. It’s great that the findings have been so well received across the NHS and around the world.

Professor Tom Robinson, NIHR Clinical Research Network National Specialty Lead for Stroke

Key publication

  • Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage CS Anderson et al. 2013; 368: 2355-65. The New England Journal of Medicine