Clinical trial end points focused on reducing mortality and morbidity in SCD in low-resource settings
| Research focus . | Attributable risk factors . | Clinical trial end points for low-resource settings . |
|---|---|---|
| Reducing mortality in SCD in low-resource settings | ||
| Reducing <5-y-old mortality | Unknown natural history of SCD in SSA; infections (malaria and invasive bacteria); splenic sequestration and severe anemia; severe malnutrition and diarrheal illnesses | Newborn screening programs to better estimate number of patients affected, survival, and complication rates. This needs to be coupled with comprehensive care programs. Estimate impact of antimalarial prophylaxis; vaccination for common bacterial infections and penicillin prophylaxis until at least 5 y; and improved nutrition, and interventions against diarrheal illnesses. |
| Reducing pregnancy-associated mortality | Increased risks of both SCD-specific and pregnancy-related complications (maternal death rate of SCD is 7%-12%) | Multidisciplinary interventions to reduce and manage hypertensive disorders of pregnancy (preeclampsia, eclampsia), severe anemia and urinary tract infections, antenatal and postnatal-acute pain episodes, and pregnancy-associated VTE |
| Reducing perioperative mortality | Poor transfusion practices; perioperative supportive care; postoperative infections | Reducing risk of transmission of transfusion associated infections; local interventions to reduce ACS postoperative complications; reduction in postoperative VTE |
| Organ-specific clinic trial end points in low-resource setting | ||
| PH | Composite model: TRV >2.5 m/s and either NT-pro-BNP ≥160 pg/mL or 6-min <330 m | Mortality from PH exercise capacity (6-min walk test; change in distance walked) |
| ACS | Define ACS based on current accepted definition (definition of a new pulmonary infiltrate (excluding atelectasis) and chest pain, fever, tachypnea, wheezing, or cough | Percentage of patients who develop ACS based on modified criteria and adjudicated |
| CKD | Severe albuminuria (>300 mg/g); moderate albuminuria (30-300 mg/g); CKD (stage >3 by GFR; stage >1) | Urine albumin/creatinine (% decrease in proteinuria); measured or estimated GFR (percentage of patients who require initiation of renal replacement therapy); progression in stage of CKD |
| Primary stroke prevention | Increased risk of stroke in children in low-resource setting (10%-11%); increased incidence of causes of severe anemia (malaria, iron deficiency anemia, severe malnutrition) | Reduction in TCD velocity in children; clinical and imaging evidence of new stroke, TIA, or death; neurocognitive testing, locally adapted Pediatric NIH Stroke Scale |
| Secondary stroke prevention | Increased risk of stroke in children in low-resource settings (10%-11%); increased incidence of causes of severe anemia (malaria, iron deficiency anemia, severe malnutrition); lack of and availability of safe transfusion practices; unavailability of disease-modifying therapy (hydroxyurea) | Prevalence of recurrent stroke: NIH stroke scale (questionnaire); clinical and imaging evidence of recurrent stroke, TIA, or death; neurocognitive testing (NIH scale) |
| Therapeutic trials: relevant clinic trial end points in low-resource settings | ||
| Phase 2 study of novel agents | Pharmacokinetics and pharmacodynamics studies; safety and efficacy of new agents; effect on splenic and renal function; biological and hematologic correlates (HbF level, reduction of intracellular Hb concentration, increasing nitrous oxide bioavailability); antiplatelet, anti-inflammatory, anticoagulation, and antiadhesion properties | Improvement in baseline Hgb, acute pain episodes rate, hematologic toxicities or serious adverse events, biological and hematologic correlates, other clinical end points: ACS, ischemic stroke, CKD, priapism, PH, leg ulcers, avascular necrosis |
| Research focus . | Attributable risk factors . | Clinical trial end points for low-resource settings . |
|---|---|---|
| Reducing mortality in SCD in low-resource settings | ||
| Reducing <5-y-old mortality | Unknown natural history of SCD in SSA; infections (malaria and invasive bacteria); splenic sequestration and severe anemia; severe malnutrition and diarrheal illnesses | Newborn screening programs to better estimate number of patients affected, survival, and complication rates. This needs to be coupled with comprehensive care programs. Estimate impact of antimalarial prophylaxis; vaccination for common bacterial infections and penicillin prophylaxis until at least 5 y; and improved nutrition, and interventions against diarrheal illnesses. |
| Reducing pregnancy-associated mortality | Increased risks of both SCD-specific and pregnancy-related complications (maternal death rate of SCD is 7%-12%) | Multidisciplinary interventions to reduce and manage hypertensive disorders of pregnancy (preeclampsia, eclampsia), severe anemia and urinary tract infections, antenatal and postnatal-acute pain episodes, and pregnancy-associated VTE |
| Reducing perioperative mortality | Poor transfusion practices; perioperative supportive care; postoperative infections | Reducing risk of transmission of transfusion associated infections; local interventions to reduce ACS postoperative complications; reduction in postoperative VTE |
| Organ-specific clinic trial end points in low-resource setting | ||
| PH | Composite model: TRV >2.5 m/s and either NT-pro-BNP ≥160 pg/mL or 6-min <330 m | Mortality from PH exercise capacity (6-min walk test; change in distance walked) |
| ACS | Define ACS based on current accepted definition (definition of a new pulmonary infiltrate (excluding atelectasis) and chest pain, fever, tachypnea, wheezing, or cough | Percentage of patients who develop ACS based on modified criteria and adjudicated |
| CKD | Severe albuminuria (>300 mg/g); moderate albuminuria (30-300 mg/g); CKD (stage >3 by GFR; stage >1) | Urine albumin/creatinine (% decrease in proteinuria); measured or estimated GFR (percentage of patients who require initiation of renal replacement therapy); progression in stage of CKD |
| Primary stroke prevention | Increased risk of stroke in children in low-resource setting (10%-11%); increased incidence of causes of severe anemia (malaria, iron deficiency anemia, severe malnutrition) | Reduction in TCD velocity in children; clinical and imaging evidence of new stroke, TIA, or death; neurocognitive testing, locally adapted Pediatric NIH Stroke Scale |
| Secondary stroke prevention | Increased risk of stroke in children in low-resource settings (10%-11%); increased incidence of causes of severe anemia (malaria, iron deficiency anemia, severe malnutrition); lack of and availability of safe transfusion practices; unavailability of disease-modifying therapy (hydroxyurea) | Prevalence of recurrent stroke: NIH stroke scale (questionnaire); clinical and imaging evidence of recurrent stroke, TIA, or death; neurocognitive testing (NIH scale) |
| Therapeutic trials: relevant clinic trial end points in low-resource settings | ||
| Phase 2 study of novel agents | Pharmacokinetics and pharmacodynamics studies; safety and efficacy of new agents; effect on splenic and renal function; biological and hematologic correlates (HbF level, reduction of intracellular Hb concentration, increasing nitrous oxide bioavailability); antiplatelet, anti-inflammatory, anticoagulation, and antiadhesion properties | Improvement in baseline Hgb, acute pain episodes rate, hematologic toxicities or serious adverse events, biological and hematologic correlates, other clinical end points: ACS, ischemic stroke, CKD, priapism, PH, leg ulcers, avascular necrosis |
NIH, National Institutes of Health; TCD, transcranial Doppler; TIA, transient ischemic attack.