Ongoing trials
There are several ongoing studies testing the feasibility and efficacy of stem cell therapies for single ventricle diseases such as HLHS. These trials focus on what are the most effective stem cells, what is the best timing in the 3-stage repair, and what is the optimal delivery method. Phase IIb trial testing the efficacy of intramyocardial injections umbilical cord blood cells during Stage II (Glenn) repair. Phase I trial testing the efficacy of autologous cord blood cell infusion during Stage 1 (Norwood) repair within two-to-three days of birth. The ELPIS trial is a phase I/IIb open pilot testing the efficacy and safety of intramyocardial donor human mesenchymal stem cell injections in patients during Stage 2 (Glenn) and Stage 3 (Fontan) repairs. Phase I trial testing the efficacy of umbilical cord blood intramyocardial injections during Stage 2 (Glenn) repair. The PERSEUS study is a phase II trial testing the efficacy of intracoronary infusions of cardiac progenitor cells and evaluating function 3-months post-treatment. APOLLON study is a phase III clinical trial testing the efficacy and safety of intracoronary injections of autologous cardiac stem cells during Stage 2 (Glenn) or Stage 3 (Fontan) repair. CHILD Study is a phase I clinical trial testing the feasibility and safety of intramyocardial injections of c-kit+ cells during Stage 2 (Glenn) repair.It is important to keep in mind that patients with HLHS are at increased risk of developing heart failure as adults. It remains unknown if these potential therapies would reduce the future risk of heart failure in these patients.
Adverse effects
The most common side effects include reactions at the injection site (in up to 84% of patients) such as pain and swelling, as well as headache (up to 12%) and fever or feeling hot (in 10%). Less common side effects (under 10%) are depressive disorders, insomnia, rashes, fatigue, musculoskeletal pain, nausea, sleep disorders, and dizziness. Pharmacology
Cabotegravir is an integrase strand transfer inhibitor. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). History
The safety and efficacy of cabotegravir/rilpivirine were established through two randomized, open-label, controlled clinical trials (Trial 1/NCT02938520 and Trial 2/NCT02951052) in 1,182 HIV-infected adults who were virologically suppressed (HIV-1 RNA less than 50 copies/milliliter) before initiation of treatment with cabotegravir/rilpivirine. Participants in both trials continued to show virologic suppression at the conclusion of each study, and no clinically relevant change from baseline in CD4+ cell counts was observed. Trials were conducted at 223 sites in 24 countries including the United States.In Trial 1, participants who were never treated for the infection before, received an approved therapy for 20 weeks. Those who did well after this treatment (who had HIV-1 RNA less than 50 copies/milliliter) were then randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks.