Prescription of concomitant medications in patients treated with Nifurtimox Eflornithine Combination Therapy (NECT) for T.b. gambiense second stage sleeping sickness in the Democratic Republic of the Congo

Background: Nifurtimox eflornithine combination therapy (NECT) to treat human African trypanosomiasis (HAT), commonly called sleeping sickness, was added to the World Health Organisation’s (WHO) Essential Medicines List in 2009 and to the Paediatric List in 2012. NECT was further tested and documented in a phase IIIb clinical trial in the Democratic Republic of Congo (DRC) assessing the safety, effectiveness, and feasibility of implementation under field conditions (NECT-FIELD study). This trial brought a unique possibility to examine concomitant drug management. Methodology/Principal findings: This is a secondary analysis of the NECT-FIELD study where 629 second stage gambiense HAT patients were treated with NECT, including children and pregnant and breastfeeding women in six general reference hospitals located in two provinces. Concomitant drugs were prescribed by the local investigators as needed. Patients underwent daily evaluations, including vital signs, physical examination, and adverse event monitoring. Concomitant medication was documented from admission to discharge. Patients’ clinical profiles on admission and safety profile during specific HAT treatment were similar to previously published reports. Prescribed concomitant medications administered during the hospitalization period, before, during, and immediately after NECT treatment, were mainly analgesics/antipyretics, anthelmintics, antimalarials, antiemetics, and sedatives. Use of antibiotics was reasonable and antibiotics were often prescribed to treat cellulitis and respiratory tract infections. Prevention and treatment of neurological conditions such as convulsions, loss of consciousness, and coma was used in approximately 5% of patients. Conclusions/Significance: The prescription of concomitant treatments was coherent with the clinical and safety profile of the patients. However, some prescription habits would need to be adapted in the future to the evolving available pharmacopoeia. A list of minimal essential medication that should be available at no cost to patients in treatment wards is proposed to help the different actors to plan, manage, and adequately fund drug supplies for advanced HAT infected patients. Trial registration number: The initial study was registered at ClinicalTrials.gov, number NCT00906880. Author summary: Sleeping sickness is a neglected tropical disease caused by a parasite, the trypanosome, transmitted by the tse-tse fly. It affects people in Sub-Saharan Africa, most of them living in poor rural settings with limited access to healthcare. If the disease remains untreated, it usually progresses from a haemo-lymphatic invasion into a second stage or neuro-encephalitic infection evolving into coma and death. When these second stage patients are referred to treatment centres, the disease is often advanced. Therefore, on top of sleeping sickness treatment, additional care and medications are regularly required. We report here the concomitant medications that were prescribed to second stage sleeping sickness patients, including vulnerable populations such as children, and pregnant and breastfeeding women, in the context of a phase IIIb trial assessing the safety, effectiveness, and feasibility of implementation of the Nifurtimox Eflornithine Combination Therapy (NECT) in field conditions. Our objective is to provide evidence to national health systems or private actors to plan and fund their essential medicine supplies adapted to second stage sleeping sickness patients.