Trial Drug Eases Sickle Cell Pain
Study: Freeing up blood flow shortens bouts of severe discomfort
TUESDAY, Nov. 6, 2001 (HealthDayNews) -- An experimental drug that reduces the sticky friction of blood flow can help alleviate the debilitating pain of sickle cell anemia, a new trial shows.
The drug, called purified poloxamer 188, or Flocor, cuts the duration of severe pain bouts by an average of eight hours, the study says -- not much on the clock but significant for sufferers. The effect was even greater in children and in patients who combined it with another medication proven to help treat symptoms of the potentially deadly blood cell disease.
Sickle cell anemia is a disease that primarily strikes American and African blacks. It involves a gene mutation in oxygen-carrying hemoglobin molecules that makes red blood cells arc, thus resembling a sickle. In this shape, they tend to clump up in small vessels, obstructing blood flow and causing swelling and excruciating pain throughout the body.
The Sickle Cell Disease Association of America says 2.5 million Americans carry one sickle cell gene, and 70,000 have the disease.
One of the worst symptoms of disorder is "acute painful crisis," an excruciating and prolonged period of pain that feels like a full-body toothache. Experts estimate that the typical sickle cell patient suffers several milder episodes of this every year, and one or two bouts of crisis that require a stay in the hospital.
Flocor, made by CytRx Corp., of Norcross, Ga., is believed to help relieve these symptoms by diluting blood viscosity and increasing the supply of oxygen to affected vessels.
The injected, synthetic compound changes the way blood cells move against each other and vessel linings, says J. Michael Grindel, vice president of drug development for the company. However, its precise mechanism of action isn't well understood, adds Grindel, a co-author of the study.
The latest findings, which appear in the Nov. 7 issue of the Journal of the American Medical Association, come from a nationwide study of the drug. A research team led by Dr. Eugene Orringer of the University of North Carolina in Chapel Hill tested Flocor in 127 sickle cell patients, ages 9 to 53, between 1998 and 1999 at 40 clinics. They also included 128 patients who received an inactive substance for the purposes of comparison.
Patients who took Flocor had an average duration of pain episodes of 133 hours, the researchers say, compared with 141 hours in the placebo group -- or 5.5 days vs. 5.9 days, respectively. Sixty-five percent of those on the drug attained resolution of the pain crisis in a week, as opposed to only 37 percent in the untreated group.
The results were more promising for children 15 and younger in the Flocor group: their pain crises were shortened by almost a full day. And almost 60 percent of them achieved pain resolution in a week, compared with 29 percent of those in the placebo group.
This evidence suggests the disease may be different for adults and children, the researchers say. "It is possible that children exhibit a better response to [Flocor] because they have less overall tissue and organ damage due to previous crises and experience less chronic pain, thereby making more evident the rheologic and anti-inflammatory effects of [the drug]," the authors write. Rheology is the study of flows.
The combination of Flocor and another sickle cell drug, hydroxyurea, led to even shorter bouts of acute pain.
Grindel says CytRx, which helped sponsor the latest study, is now seeking government funding for a second trial, this one in children alone. Results from that trial aren't expected for three to four years, he says.
But Dr. Ronald Nagel, a blood specialist at the Albert Einstein College of Medicine in New York City, says he's not especially impressed with Flocor's performance so far. "It think the effect is very modest. The worst part is that since they don't know the mechanism of the drug, there's no way of proving it [works]. And they don't know how to tinker with it and make it better."
On the other hand, says Nagel, who also holds a post at New York's Montefiore Medical Center, "There is one thing that everybody could do now that would impact tremendously: Do correct pain treatment."
Unfortunately, Nagel adds, pain care is mainly administered by non-specialists and comes too late to make a difference in the course of an acute crisis. After all, most sickle cell patients go to the emergency room when they feel a bout coming on and often must wait several hours before getting treated, he notes.
For that reason, Nagel helped start a special "day" clinic for these patients, with pain and sickle cell specialists on staff. A study of its usefulness found that 80 to 90 percent of patients could be sent home in under a day, compared with fewer than 40 percent treated for acute pain crises in the emergency room, he says.